Calcification Propensity and Survival among Renal Transplant Recipients

Calciprotein particle maturation time (T₅₀) in serum is a novel measure of individual blood calcification propensity. To determine the clinical relevance of T₅₀ in renal transplantation, baseline serum T₅₀ was measured in a longitudinal cohort of 699 stable renal transplant recipients and the associations of T₅₀ with mortality and graft failure were analyzed over a median follow-up of 3.1 years. Predictive value of T₅₀ was assessed for patient survival with reference to traditional (Framingham) risk factors and the calcium-phosphate product. Serum magnesium, bicarbonate, albumin, and phosphate levels were the main determinants of T₅₀, which was independent of renal function and dialysis vintage before transplant. During follow-up, 81 (12%) patients died, of which 38 (47%) died from cardiovascular causes. Furthermore, 45 (6%) patients developed graft failure. In fully adjusted models, lower T₅₀ values were independently associated with increased all-cause mortality (hazard ratio, 1.43; 95% confidence interval, 1.11 to 1.85; P=0.006 per SD decrease) and increased cardiovascular mortality (hazard ratio, 1.55; 95% confidence interval, 1.04 to 2.29; P=0.03 per SD decrease). In addition to age, sex, and eGFR, T₅₀ improved prognostication for all-cause mortality, whereas traditional risk factors or calcium-phosphate product did not. Lower T₅₀ was also associated with increased graft failure risk. The associations of T₅₀ with mortality and graft failure were confirmed in an independent replication cohort. In conclusion, reduced serum T₅₀ was associated with increased risk of all-cause mortality, cardiovascular mortality, and graft failure and, of all tested parameters, displayed the strongest association with all-cause mortality in these transplant recipients.     

Renal Allograft Survival in Transplant Recipients with Focal Segmental Glomerulosclerosis

Previous literature suggests that the recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation is more common in recipients who have received an HLA-identical living-related (LRD) transplant. To address the question if FSGS patients can safely receive a 6-antigen match LRD kidney transplant, we analyzed death-censored renal allograft survival data of FSGS patients from the United States Renal Data System database (USRDS). Using the USRDS and the U.S. Scientific Renal Transplant Registry between the years 1988-97, we found 19259 adult primary renal transplant recipients, of which 2414 patients had FSGS as their primary diagnosis as compared to 16845 patients who had other types of glomerulonephritis (GN). A Cox proportional hazard model was used to estimate death-censored graft survival among FSGS patients with a zero mismatch LRD kidney transplant. The model included a triple interaction term comparing FSGS vs. GN vs. living donation (LD) vs. cadaveric donation (CAD) vs. zero mismatch (six antigen or HLA-identical) vs. mismatch. Annually adjusted death censored graft loss rates per 1000 patients (ADGL) were calculated. Focal segmental glomerulosclerosis patients receiving a zero mismatch LRD kidney transplant had the lowest ADGL rate, losing 10.5 grafts per 1000 patients per year. Not significantly different but higher (14.3) was the ADGL rate for LD, zero mismatch GN recipients. The ADGL rate was significantly higher in FSGS recipients who received a LD, mismatched transplant (36.5). Focal segmental glomerulosclerosis patients who received a CAD, zero mismatched graft (44.1), or CAD, mismatched graft (63.2), had significantly higher ADGL rates. Zero mismatch LRD kidney transplants are not a risk factor for graft loss in FSGS patients but are associated with significantly better death-censored graft survival as compared to CAD 6-antigen match or mismatched donations.     

Early Assessment of Renal Resistance Index and Long-Term Renal Function in Renal Transplant Recipients

Background. The effect of the intrarenal arterial resistance index (RI) on long-term renal functions is not well known. We examined the predictive value of intrarenal RI on long-term allograft outcomes. Methods. We retrospectively investigated 121 stable renal transplant recipients, followed for a mean of 63.21?±?19.9 months after renal transplant. Patients with complications during the first six months after transplant were not included. Color Doppler ultrasonography was done to calculate the intrarenal RI within the first four weeks after transplant. Results. Older recipient age, high pulse pressure, active smoking, and proteinuria were associated with a higher intrarenal RI. Multivariate analyses revealed that renal RI and donor age were independent predictors of allograft outcome. Kaplan-Meier estimates of cumulative graft survival were significantly worse in patients who had an RI of 0.7 or more than they were in patients who had an RI of less than 0.7 (p?=?.005). Development of chronic allograft nephropathy (CAN) was significantly higher in patients who had an RI of 0.7 or more (p?=?.02). Conclusions. Renal RI determined within the first month after renal transplant predicts long-term allograft function and development of CAN in renal transplant recipients.     

Pregnancy in Renal Transplant Recipients

Objective

Renal transplantation with a well-functioning graft leads to a rapid restoration of endocrine and sexual functions. The aim of this study was to examine our experience with pregnancies among renal transplant patients, particularly with regard to their impact on graft function.

Patients and Methods

We analyzed 10 pregnancies in 7 renal transplant recipients for long-term graft outcomes in terms of clinical and biological data.

Results

The mean patient age was 28.5 ± 4 years. They all received a living donor kidney. The time between transplantation and the onset of pregnancy was 33.4 ± 23.2 months. Regarding the immunosuppressive therapy, all patients received steroids and cyclosporine; 4 patients received in addition azathioprine and 2 received mycophenolate mofetil that was changed at 1 month before conception to azathioprine. There was no significant difference between the serum creatinine before and during pregnancy. We did not observe any acute rejection episode. Pregnancy complications were preclampsia in 1 case, hypertension in 1 case, urinary tract infection in 2 cases, and anemia in 80% of patients during the third trimester. Premature rupture of membranes occurred in 1 case and preterm delivery in 2 cases. Two cases of neonatal death were registered. Cesarean section was performed in 50% of cases. The follow-up revealed 2 cases of chronic rejection.

Conclusion

A multidisciplinary approach is necessary for pregnancy which generally occurs at 2 years after kidney transplantation.     

Demodicosis in Renal Transplant Recipients

Solid organ transplant recipients have an increased incidence of skin infections resulting from immunosuppression. Common pathogens include herpes simplex virus, varicella zoster virus, Gram‐positive bacteria and dermatophytes; however, the contribution of multicellular parasitic organisms to dermatologic disease in this population remains less studied. Demodex folliculorum and brevis are commensal mites that reside on human skin. Proliferation of Demodex mites, or demodicosis, is associated with rosacea and rosacea‐like disorders, particularly in immunocompromised populations, although their ability to cause disease is still the subject of debate. We present a case series of four renal transplant recipients with the singular chief complaint of acne rosacea who we diagnosed with demodicosis. Although one of the four patients showed complete resolution following initial antiparasitic therapy, the other three required subsequent antibacterial treatment to fully resolve their lesions. We suggest that demodicosis may be more prevalent than once thought in solid organ transplant recipients and showed that Demodex‐associated acne rosacea can be effectively treated in this population.     

Hyperhomocysteinemia in Renal Transplant Recipients

Renal transplantation is a commonly performed curative procedure for end-stage renal disease. With the increase in renal allograft half-lives, attention is now being focused on cardiovascular morbidity and death in the renal transplant recipient (RTR) population. Among the more novel cardiovascular disease (CVD) risk factors for which this group is at risk is hyperhomocysteinemia. Hyperhomocysteinemia has been associated with an increased risk of CVD, although prospective randomized trials designed to prove causality are still ongoing. Since plasma total homocysteine levels are inversely related to renal function, RTRs have a greatly increased prevalence of hyperhomocysteinemia. Other determinants of homocysteine include B-vitamins, albumin, age, and genetic polymorphisms. Although RTRs are resistant to the typical B-vitamin doses used to correct hyperhomocysteinemia in the general population, they do respond to supraphysiologic dose therapy. In terms of prevalence, etiology, and treatment of hyperhomocysteinemia, RTRs are very similar to the much larger chronic renal insufficiency population. For this reason, RTRs have been chosen as an ideal study population in investigating the effect of reducing hyperhomocysteinemia on CVD outcomes.     

Serum Procalcitonin Correlates With Renal Function and Immune Components in Early-Stage Renal Transplant Recipients

BackgroundIn renal transplantation, monitoring procalcitonin (PCT) in the early post-transplant period can be a promising method for early tracking of infectious complications. However, the correlation between PCT and infection-related factors and immune components and renal function remains unclear.Patients and methodsBetween November 2017 and December 2018, 62 early-stage renal transplant recipients were selected, and 4 mL peripheral blood samples were collected to detect the changes of specific immune cells and cytokines. Our study was in compliance with the Helsinki Congress and the Declaration of Istanbul; no prisoners were used, and participants were neither paid nor coerced in our study.ResultsAccording to serum PCT levels, recipients were divided into a high group (PCT ≥ 0.5 ng/mL) and a low group (PCT < 0.5 ng/mL). Compared with the low group, creatinine, cystatin C, urea, T helper type (Th) 22 cells, IL-22 + Th17 cells, interleukin (IL)-22, tumor necrosis factor alpha, and IL-17A increased while estimated glomerular filtration rate (eGFR) was decreased in the high group. In addition, PCT was significantly correlated with eGFR in the high group.ConclusionsSerum PCT is related with renal function and seems to be associated with immune components in early-stage renal transplant recipients.     

Low Survival Rate of Renal Transplant Recipients From Unrelated Living Donors With Renal Diseases

In three hospitals within a restricted area in Japan in November, 2006, 42 patients were revealed to have received kidneys transplanted from unrelated living donors who displayed renal diseases. All of these cases were performed by one doctor without any ethical discussion in the hospitals nor any reports to the public. Almost all medical records were discarded legally in two hospitals. Only one hospital, Uwajima City Hospital, kept the almost complete records including the survivals of 25 cases. The Japan Society for Transplantation was asked to analyze these cases leading to this report on the long-term outcome of cases at Uwajima City Hospital. The diseased kidney grafts were procured in four hospitals. The cases of removal of the kidneys from the donors were malignant diseases (n = 11) or benign diseases (n = 14). The survival rates of the donors were 86.1% at 1, 70.8% at 5, and 57.7% at 10 years. The survival rates of the recipients transplanted from donors with malignant versus benign diseases were 80.8% versus 92.3% in 1, 48.5% versus 84.6% at 5% and 48.5% versus 76.2% at 10 years, respectively. The survival rates of the grafts from donors with malignant versus benign diseases were 71.6% versus 71.4% at 1, 15.3% versus 50.0% at 5, and 15.3% versus 33.3% at 10 years, respectively. In conclusion, we have reported herein the low survival rates of renal transplantation recipients and grafts from unrelated living donors with preexistent renal diseases.     

Post Transplant Erythrocytosis in Hypercalcemic Renal Transplant Recipients

In vitro data suggest that calcium plays an important role in normal and disordered erythropoiesis. The purpose of this study is to determine whether there is an association between serum calcium, various hormone levels, and the development of post transplant erythrocytosis (PTE). Data were collected on 283 patients who underwent renal transplantation between 1994 and 1998. The relationship between serum calcium and PTE development was tested using the chi-square test. Univariate and multivariable adjusted models were employed to determine predictors of maximum hematocrit. Selected patients underwent measurement of intact parathyroid hormone (PTH), 1,25-dihydroxy vitamin D, and erythropoietin (EPO). Seventy-three patients (26%) developed PTE. Post transplant erythrocytosis was more common in patients with hypercalcemia compared with patients with normal serum calcium (34% vs. 18%, p = 0.002). In multivariable analyses, serum calcium was a strong independent predictor of maximum hematocrit post transplant, even after adjustment for renal function. A serum calcium of >or=10.2 mg/dL was associated with greater than two-fold increased odds of PTE. There were no differences in hormone levels between subjects with hypercalcemia and PTE, subjects with PTE alone, and subjects with hypercalcemia alone. Hypercalcemia is associated with the development of PTE in renal transplant recipients.     

Survival and Evolution of Renal Function in Kidney Transplant Recipients From Type II Asystolic Donations: A Single-center Experience

Background

In recent years, stagnation in the number of kidneys from after brain-dead donors (DBD) has stimulated the use of non–heart beating donors (NHBDs). Herein we present our 5-year experience with type II Maastricht NHBDs in renal transplantation.

Conversion to Everolimus in Kidney Transplant Recipients With Decreased Renal Function

Whenever graft function is good and proteinuria is under control, many reports describe the efficacy and safety of the conversion to Everolimus (EVL) among stable kidney recepients, simultaneously withdrawing the calcineurin inhibitor (CNI). However, there are few publications that evaluate the role of EVL in patients with decreased renal function. We describe our experience with 22 stable renal transplant recipients whose serum creatinine concentrations were >2 mg/dL and proteinuria <1000 mg/24 h who underwent an abrupt switch from a CNI to EVL. Conversion was simple, well-tolerated, and safe using an initial dose of 1–3 mg/d that was sufficient to achieve the recommended levels of 3–8 ng/dL. The adverse events were expected; most of them were of medium intensity. Globally, over the 24 months follow-up, there was improved renal function despite the initial creatinine. The improvement was greater when the switch was performed during the first year after transplantation. Two patients lost their grafts after a dramatic evolution with development of nephrotic syndrome and increasing creatinine. In our experience, conversion to EVL is a safe alternative among patients with chronic allograft nephropathy or nephrotoxicity due to CNI, even in patients with significantly decreased renal function at the time of the switch.     

Paradoxical Depression in Renal Transplant Recipients

Paradoxical depression occurs despite a completely successful transplantation without tissue rejection or other medical complications. In this study, the occurrence of paradoxical depression was retrospectively investigated among 1139 Japanese successful renal transplant recipients January 1997 through September 2006. Among the 1139 recipients, 103 visited the Department of Psychiatry after renal transplantation, including 40 with depressive symptoms and 15 with a physical problem considered to have nonparadoxical depression. The other 25 recipients were considered to have paradoxical depression; that is, more than half of the 40 recipients with depressive symptoms had paradoxical depression. There were no significant differences in the clinical characteristics, including average age at the time of renal transplantation, rate of living-donor transplantation, rate of ABO incompatibility, method of dialysis (hemodialysis or peritoneal dialysis), duration of dialysis, and time interval between the renal transplantation and the initial visit to the Department of Psychiatry among the 2 groups. These results suggested that there was another risk factor or interactions between factors. Of the 25 recipients, 6 had relationship problems, 6 had social-rehabilitation problems, and 13 had mentioned no clear psychological problems. These psychological factors might in fact be related to the loss of an imagined past. Additional consecutive prospective studies are needed—a challenging prospect for consultation liaison psychiatrists in the field of transplantation.     

Chickenpox in Adult Renal Transplant Recipients

Five of 610 adults developed chickenpox between 35 days and9.2 years after renal transplantation, and only one patientsurvived. All patients received prednisolone and azathioprineduring the incubation period. Corticosteroid therapy was continued,but azathioprine was stopped after diagnosis. Four patientswere treated with acyclovir, but three were given suboptimaldoses. The patient who survived had been taking the lowest doseof azathioprine and was given the recommended dose of acyclovir.All patients who died developed disseminated intravascular coagulation,and at postmortem examination were found to have had cerebralhaemorrhage. None of the patients treated with acyclovir hadevidence of active varicella-zoster virus infection at postmortem examination, but two had disseminated bacterial and fungalinfections. Chickenpox follows a severe and often fatal course in adultswith renal transplants. Prompt acyclovir therapy can be effective,provided an adequate dose is given. Attention should be directedtowards prevention by the identification and immunisation ofat risk patients prior to transplantation.     

Pulmonary Infections in Renal Transplant Recipients

Forty-six episodes of pulmonary infection occurred in 41 patients during a seven year period in which 187 renal transplants were performed in 168 patients. Thirty-seven episodes followed 152 cadaveric transplants (24.39%), and four episodes followed 35 living related donor transplants (11.4%). Five patients had two episodes of pulmonary infection. Twenty-four patients recovered, and 17 died (41.5%). Pulmonary infections appeared from two days to three years after transplantation, but predominated in the first four months (32/46). They were caused primarily by bacterial agents (74%) with protozoa, fungi, and viruses appearing less frequently. In 35 episodes, a single etiologic agent was found, but 11 were caused by two or more agents. When compared with noninfected recipients, there was no significant difference with regard to number of rejection crises, maintenance prednisone dosage, or blood glucose. However, subnormal renal function was significantly associated with the development of infection. Azathioprine dosages were actually higher for the noninfected patients, reflecting a tendency to lower the dose of azathioprine in the presence of decreased renal function. Fever was the most common presenting symptom. Transtracheal aspiration with Gram stain and direct sensitivity plating routinely provided early and accurate identification of the organism and a guide for therapy in bacterial infections. Pulmonary infection in renal transplant recipients is associated with a high mortality rate. Early diagnosis and specific treatment are essential to successful management.     

Impaired Renal Allograft Function is Associated with Increased Arterial Stiffness in Renal Transplant Recipients

It is important whether impairment of renal allograft function may deteriorate arterial stiffness in renal transplant recipients. In a cross-sectional study, arterial vascular characteristics were non-invasively determined in 48 patients with renal allograft using applanation tonometry and digital photoplethysmography. Mean age was 51 ± 2 years (mean ± SEM), and studies were performed 17 ± 1 months after transplantation. The stage of chronic kidney disease was based on the glomerular filtration rate. We observed a significant association between the stage of chronic kidney disease and arterial stiffness of large arteries S1 and small arteries S2 in renal transplant recipients (each p < 0.05 by non-parametric Kruskal–Wallis test between groups). Multivariate linear regression analysis showed that male gender of patients with renal allograft (p < 0.01) reduced glomerular filtration rate (p = 0.01), and older age of kidney donor (p = 0.04) were independently associated with an increase of large artery stiffness S1. Furthermore, a significant association between the stage of chronic kidney disease and arterial vascular reactivity during reactive hyperemia was observed (p < 0.05 by non-parametric Kruskal–Wallis test between groups). It is concluded that impairment of renal allograft function is associated with an increased arterial stiffness in renal transplant recipients.     

Effects of Elevated Tacrolimus Trough Levels in Association With Infectious Enteritis on Graft Function in Renal Transplant Recipients

Background

The bioavailability of oral tacrolimus is influenced by enterocyte metabolism, which involves CYP3A and P-glycoprotein. Viral infection–induced intestinal inflammation damages the enterocytes and causes unfavorable elevations in blood tacrolimus levels in transplant recipients, which may lead to nephrotoxicity.

Methods

From May 2000 to May 2011, 56 renal transplant recipients receiving tacrolimus at our hospital suffered from infectious enteritis with diarrhea. We investigated the tacrolimus trough levels before and after the onset of enteritis and evaluated the influence of elevated tacrolimus trough levels on the rate of changes in serum creatinine levels.

Results

Elevated tacrolimus trough levels were observed in 52 recipients (93%) after the onset of diarrhea, and the mean value was 2.3 times higher than that before the onset of enteritis (P = .0175). Tacrolimus trough levels returned to their previous levels 2 weeks after the onset of enteritis, even in recipients with >2-fold increase, following dose adjustments. Serum creatinine levels did not significantly differ between recipients with >2-fold increase in tacrolimus trough levels and those with <2-fold increase in trough levels during a 6-month period after the onset of enteritis.

Conclusions

Elevations in the tacrolimus trough levels due to infectious enteritis with diarrhea can improve in ∼2 weeks by adjusting the tacrolimus dosage. Such temporary elevations in the tacrolimus trough levels may not produce serious nephrotoxicity even in recipients with remarkably elevated trough levels.     

Urinary Retinol-Binding Protein 4 is Associated With Renal Function and Rapid Renal Function Decline in Kidney Transplant Recipients

BackgroundUrinary retinol-binding protein 4 (RBP4) has been known as a biomarker of chronic kidney disease. In this study, we evaluated the association of urinary RBP4 with renal function and progression of renal function in kidney transplant recipients (KTRs).MethodsA total 50 KTRs were included in this study. Proteomic analysis with liquid chromatography-mass spectrometry and tandem mass spectrometry was performed to discover potential urinary biomarkers. Several urinary proteins including RBP4 were identified and then validated by enzyme-linked immunosorbent assay. Rapid renal function decline was defined as estimated glomerular filtration rate (eGFR) decline of >3 mL/min/1.73 m²/year or initiation of dialysis, and 19 (38%) were included in rapid renal function decline group.ResultsUrinary RBP4/creatinine was inversely correlated with allograft function (r = –0.54, P < .001 with eGFR, and r = 0.49, P < .001 with serum creatinine, respectively). Urinary RBP4/creatinine was higher in rapid renal function decline group than in stable renal function group (184.9 ± 156.7 vs 83.1 ± 99.9, P = .017). Log-transformed urinary RBP4/creatinine was significantly associated with rapid renal function decline in univariate logistic regression analysis (Odds ratio [OR] 7.59, confidence interval [CI] 2.04-36.70, P = .005). In multivariate logistic regression adjusted with recipient age and sex, donor age, number of HLA mismatch, and acute rejection episode, urinary RBP4/creatinine remained a significant factor for rapid renal function decline (OR 9.43, CI 1.99-65.65, P = .010). Receiver operating characteristic analysis showed that the area under the curve of urinary RBP4/creatinine was 0.747 (CI 0.608-0.886, P < .001) for rapid renal function decline.ConclusionsUrinary RBP4 levels are associated with renal function and might be used to predict rapid renal function decline in KTRs.     

Thrombophilic Mutations: No Association With Thrombotic Events in Renal Transplant Recipients

Factor V Leiden and mutation of prothrombin gene G20210A have been associated with poor results in the early post-kidney transplantation period. Its long-term importance in stable patients has yet to be evaluated. We studied the prevalence of these inherited mutations and their relationship to thrombotic events in 82 Argentine renal transplant recipients with adequate long-term kidney function. In aggregate, 7.2% of patients were carriers of these mutations; however, their presence did not show any association with thrombotic events or renal function alterations. The routine evaluation for these mutations does not seem to be cost-effective in renal transplant patients.