Do Infectious Diseases After Kidney Retransplantation Differ From Those After First Kidney Transplantation?

Background: Infectious diseases (IDs) are highly relevant after solid organ transplantation in terms of morbidity and mortality, being among the most common causes of death. Patients undergoing kidney retransplantation (re-K-Tx) have been already receiving immunosuppressive therapy over a prolonged period, potentially facilitating subsequent infections. Comparing ID events after re-K-Tx and first kidney transplantation (f-K-Tx) can delineate patterns and risks of ID events associated with prolonged immunosuppression. Methods: We included adult patients with records on f-K-Tx and re-K-Tx in the Swiss Transplant Cohort Study. We analyzed ID events after f-K-Tx and re-K-Tx within the same patients and compared infection rates, causative pathogens, and infection sites. Recurrent time-to-event analyses were performed for comparison of infection rates. Results: A total of 59 patients with a median age of 47 years (range, 18-73) were included. Overall, 312 ID events in 52 patients occurred. In multivariable recurrent event modeling, the rate of ID events was significantly lower after re-K-Tx (hazard ratio, 0.70; P = .02). More bacterial (68.9% vs 60.4%) and fungal (4.0% vs 1.1%) infections were observed after f-K-Tx but fewer viral infections (27.0% vs 38.5%) as compared with re-K-Tx (P = .11). After f-K-Tx, urinary and gastrointestinal tract infections were more frequent; after re-K-Tx, respiratory tract and surgical site infections were more frequent (P < .001). Conclusions: ID events were less frequent after re-K-Tx. Affected sites differed significantly after f-K-Tx vs re-K-Tx.

[OCT, Triple H or anything else?] / OCT, Triple H oder doch etwas anderes?

Hyperammonemia is a life-threatening condition, the prognosis of which depends on a rapid reduction of ammonia. If a hepatic cause is excluded, the differential diagnosis is broad and even in adulthood includes hereditary metabolic diseases. Here, the case of a 25-year-old female patient with severe hyperammonemia refractory to standard therapy is described and the relevance of extracorporeal elimination of ammonia emphasized.

Surgical site infections after kidney transplantation are independently associated with graft loss.

Surgical site infections (SSIs) are common health care-associated infections. SSIs after kidney transplantation (K-Tx) can endanger patient and allograft survival. Multicenter studies on this early posttransplant complication are scarce. We analyzed consecutive adult K-Tx recipients enrolled in the Swiss Transplant Cohort Study who received a K-Tx between May 2008 and September 2020. All data were prospectively collected with the exception of the categorization of SSI which was performed retrospectively according to the Centers for Disease Control and Prevention criteria. A total of 58 out of 3059 (1.9%) K-Tx recipients were affected by SSIs. Deep incisional (15, 25.9%) and organ/space infections (34, 58.6%) predominated. In the majority of SSIs (52, 89.6%), bacteria were detected, most frequently Escherichia coli (15, 28.9%), Enterococcus spp. (14, 26.9%), and coagulase-negative staphylococci (13, 25.0%). A BMI ≥25 kg/m2 (multivariable OR 2.16, 95% CI 1.07-4.34, P = .023) and delayed graft function (multivariable OR 2.88, 95% CI 1.56-5.34, P = .001) were independent risk factors for SSI. In Cox proportional hazard models, SSI was independently associated with graft loss (multivariable HR 3.75, 95% CI 1.35-10.38, P = .011). In conclusion, SSI was a rare complication after K-Tx. BMI ≥25 kg/m2 and delayed graft function were independent risk factors. SSIs were independently associated with graft loss.

Long-term patency of arteriovenous fistulas for hemodialysis: A decade's experience in a transplant unit.

BACKGROUND: The heterogeneous quality of studies on arteriovenous fistulas outcome, with variable clinical settings and large variations in definitions of patency and failure rates, leads to frequent misinterpretations and overestimation of arteriovenous fistula patency. Hence, this study aimed to provide realistic and clinically relevant long-term arteriovenous fistula outcomes. METHODS: We retrospectively analyzed all autologous arteriovenous fistulas at our center over a 10-year period (2012-2022). Primary and secondary patency analysis was conducted using the Kaplan-Meier method; multivariate analysis of variance was used to detect outcome predictors. Vascular access-specific endpoints were defined according to the European guidelines on vascular access formation. FINDINGS: Of 312 arteriovenous fistulas, 57.5% (n = 181) were radio-cephalic (RC_AVF), 35.2% (n = 111) brachio-cephalic (BC_AVF), and 6.3% (n = 20) brachio-basilic (BB_AVF). 6, 12, and 24 months follow-up was available in 290 (92.1%), 282 (89.5%), and 259 (82.2%) patients, respectively. Primary patency rates at 6, 12, and 24 months were 39.5%, 34.8%, and 27.2% for RC_AVF, 58.3%, 44.4%, and 27.8% for BC_AVF, and 40.0%, 42.1%, and 22.2% for BB_AVF (p = 0.15). Secondary patency rates at 6, 12, and 24 months were 65.7%, 63.8%, and 59.0% for RC_AVF, 77.7%, 72.0%, and 59.6% for BC_AVF, and 65.0%, 68.4%, and 61.1% for BB_AVF (p = 0.29). Factors associated with lower primary and secondary patency were hemodialysis at time of arteriovenous fistula formation (p = 0.037 and p = 0.024, respectively) and higher Charlson Comorbidity Index (p = 0.036 and p < 0.001, respectively). Previous kidney transplant showed inferior primary patency (p = 0.005); higher age inferior secondary patency (p < 0.001). DISCUSSION: Vascular access care remains challenging and salvage interventions are often needed to achieve maturation or maintain patency. Strict adherence to standardized outcome reporting in vascular access surgery paints a more realistic picture of arteriovenous fistula patency and enables reliable intercenter comparison.

Peritransplant Varicosis After Simultaneous Pancreas and Kidney Transplantation Is an Uncommon Cause of Late-Onset and Recurrent Gastrointestinal Bleeding.

Ectopic peritransplant varicosis represents an uncommon cause of late-onset gastrointestinal (GI) bleeding after simultaneous pancreas and kidney transplantation (SPK). We report on a 53-year-old female patient who suffered from recurrent upper GI bleeding seven years after SPK with persistent graft function. Upper endoscopy revealed perianastomotic angiodysplasias, treated by clipping and Argon-Plasma-Coagulation. Repeated endoscopy showed no signs of anastomotic ulcer. With persistent symptoms, computed tomography and angiography revealed extensive ectopic varicosis around the pancreas and duodenal graft. With no signs of portal hypertension, pancreas graft venous outflow impairment or arterio-venous fistula, the origin of variceal formation remained unknown. The extended finding did not allow for endovascular treatment by embolization. Surgery with extensive variceal ligation led to persistent cessation of hemorrhage and maintained stable graft function. In patients with unclear recurrent upper GI bleeding after SPK, one should consider ectopic peritransplant varicosis as an exceptional bleeding cause. If endoscopic treatments fail, angiography should be performed to rule out unusual causes of vascular complications. In case of extensive peritransplant varicosis, surgery may remain the only successful therapy, whenever possible including graft preservation in well-functioning grafts.

Impact of Hyponatremia after Renal Transplantation on Decline of Renal Function, Graft Loss and Patient Survival: A Prospective Cohort Study.

BACKGROUND: Hyponatremia is one of the most common electrolyte disorders observed in hospitalized and ambulatory patients. Hyponatremia is associated with increased falls, fractures, prolonged hospitalisation and mortality. The clinical importance of hyponatremia in the renal transplant field is not well established, so the aim of this study was to determine the relationships between hyponatremia and mortality as main outcome and renal function decline and graft loss as secondary outcome among a prospective cohort of renal transplant recipients. METHODS: This prospective cohort study included 1315 patients between 1 May 2008 and 31 December 2014. Hyponatremia was defined as sodium concentration below 136 mmol/L at 6 months after transplantation. The main endpoint was mortality. A secondary composite endpoint was also defined as: rapid decline in renal function (≥5 mL/min/1.73 m2 drop of the eGFR/year), graft loss or mortality. RESULTS: Mean sodium was 140 ± 3.08 mmol/L. 97 patients displayed hyponatremia with a mean of 132.9 ± 3.05 mmol/L. Hyponatremia at 6 months after transplantation was associated neither with mortality (HR: 1.02; p = 0.97, 95% CI: 0.47-2.19), nor with the composite outcome defined as rapid decline in renal function, graft loss or mortality (logrank test p = 0.9). CONCLUSIONS: Hyponatremia 6 months after transplantation is not associated with mortality in kidney allograft patients.

Safety of Kidney Biopsy when Performed as an Outpatient Procedure.

INTRODUCTION: Kidney biopsy remains the gold standard for the diagnosis of most renal diseases. A major obstacle to performing a biopsy is safety concerns. However, many safety measures are not evidence based and therefore vary widely between centers. We sought to determine the rate and timing of kidney biopsy complications in our center, to compare the complication rate between native and transplant kidney biopsies, to evaluate the feasibility of performing kidney biopsies as an outpatient procedure and the value of a postbiopsy ultrasound before discharge, and to identify risk factors for complications. METHODS: We performed a single-center, retrospective, observational study at the Division of Nephrology of the University Hospital Zurich including all patients who underwent renal biopsy between January 2005 and December 2017. Major bleeding (primary outcome) and any other bleeding or nonbleeding complications (secondary outcomes) were compared between native and transplant kidney biopsies and between inpatient and outpatient procedures and correlated with clinical factors possibly affecting bleeding risk. RESULTS: Overall, 2,239 biopsies were performed in 1,468 patients, 732 as inpatient and 1,507 as outpatient procedures. Major bleeding was observed in 28 (3.8%) inpatient and in 15 (1.0%) outpatient procedures, totaling to 43 (1.9%) of all biopsies. Major bleeding requiring intervention amounted to 1.0% (0.5% of outpatient procedures). Rate of major bleeding was similar between native and transplant kidneys. 13/15 (87%) bleeding episodes in planned outpatient procedures were detected during the 4-h surveillance period. Risk factors for bleeding were aspirin use, low eGFR, anemia, cirrhosis, and amyloidosis. Routine postbiopsy ultrasound did not change management. CONCLUSIONS: Kidney biopsy is an overall safe procedure and can be performed as an outpatient procedure in most patients with an observation period as short as 4 h. The value of routine postbiopsy ultrasound is questionable.

Adherence to, and patient convenience of, prolonged-release tacrolimus in stable kidney and liver transplant recipients after conversion from immediate-release tacrolimus in routine clinical practice in Switzerland.

AIMS OF THE STUDY: Non-adherence to immunosuppressive therapy in patients following solid organ transplantation is associated with an increased risk of transplant rejection and graft loss. A high pill burden can adversely affect patients’ implementation of their treatment regimens and may lead to omitting doses of medication. The aim of this study was to investigate medication implementation adherence in liver and kidney transplant recipients converted from twice-daily, immediate-release tacrolimus to once-daily, prolonged-release tacrolimus. METHODS: This multicentre, non-interventional, observational, 12-month study evaluated implementation adherence in routine practice at five hospitals in Switzerland. Patients attended four clinical visits: at baseline (pre-conversion), and then at week 2, month 6 and month 12 post-conversion. Implementation was defined as consistently taking medication at the correct time and at the correct dose in order to achieve target tacrolimus trough levels. Implementation adherence was evaluated in three ways: using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) interview questionnaire (at baseline and month 12), investigator-rated patient adherence (recorded at all visits), and tacrolimus trough levels (assessed throughout the study; sub-therapeutic levels were predefined by the investigator on an individual patient basis, over-therapeutic levels were defined as tacrolimus trough levels >15 ng/ml). The primary composite endpoint was non-adherence according to the BAASIS at month 12, any post-conversion investigator adherence rating of “poor”, or sub-therapeutic or over-therapeutic tacrolimus trough levels at month 6 or 12. Secondary endpoints included: individual components of the composite non-adherence primary endpoint, tacrolimus pill burden, patient satisfaction, and adverse drug reactions. RESULTS: Seventy-five patients received prolonged-release tacrolimus; 68 patients (46 kidney and 22 liver transplant recipients) completed the study. Of these 68 patients, 24 had missing data for at least one component of the primary endpoint; therefore, data for the primary composite endpoint were evaluable for 44 patients. Most (81.8%; 36/44) patients were non-adherent for the composite endpoint. Sub-therapeutic tacrolimus trough levels outside of the predefined therapeutic range were the largest contributor to the composite endpoint, and were detected in 62.0% (31/50) of patients. Overall non-adherence according to the BAASIS was similar pre-conversion (30.7%) and at 12 months post-conversion (28.3%). Investigators rated adherence as “poor” for two patients. Prolonged-release tacrolimus decreased tacrolimus pill burden in 66.7% of patients. All patients were very satisfied / satisfied with prolonged-release tacrolimus; 75.0% found it easier to remember to take prolonged-release versus immediate-release tacrolimus. Twenty percent of patients reported adverse drug reactions, with infections being the most frequently reported (9.3%). CONCLUSION: Overall, 1-year non-adherence rates were similar following conversion from immediate-release to prolonged-release tacrolimus; however, prolonged-release tacrolimus intake was more convenient. No new safety signals were detected.

Predictive Power of Bone Turnover Biomarkers to Estimate Bone Mineral Density after Kidney Transplantation with or without Denosumab: A post hoc Analysis of the POSTOP Study.

BACKGROUND: Low bone mineral density (BMD) represents a major risk factor for bone fractures in patients with chronic kidney disease (CKD) as well as after kidney transplantation. However, modalities to solidly predict patients at fracture risk are yet to be defined. Better understanding of bone turnover biomarkers (BTMs) may close this diagnostic gap. This study strives to correlate BTMs to BMD in kidney transplant recipients. METHODS: Changes in BTMs - procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSAP), ß-isomer of the C-terminal telopeptide of type I collagen, and urine deoxypyridinoline/Cr - at the time of transplant and 3 months were correlated to changes in BMD measured by dual-energy X-ray absorptiometry at the time of transplant, 6, and 12 months, respectively. Half of the collective was treated with denosumab twice yearly in addition to the standard treatment with calcium and vitamin D. RESULTS: Changes in bone formation markers BSAP and P1NP within 3 months showed a significant negative correlation to changes in BMD at the hip within 6 months in denosumab-naïve patients. This correlation was abrogated by denosumab treatment. CONCLUSIONS: Changes in BSAP and P1NP showed promise in short-term prediction of BMD. We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.

Dialysis after graft loss: a Swiss experience.

BACKGROUND: Patients returning to dialysis after graft loss have high early morbidity and mortality. METHODS: We used data from the Swiss Transplant Cohort Study to describe the current practice and outcomes in Switzerland. All patients who received a renal allograft between May 2008 and December 2014 were included. The patients with graft loss were divided into two groups depending on whether the graft loss occurred within 1 year after transplantation (early graft loss group) or later (late graft loss group). Patients with primary non-function who never gained graft function were excluded. RESULTS: Seventy-seven out of 1502 patients lost their graft during follow-up, 40 within 1 year after transplantation. Eleven patients died within 30 days after allograft loss. Patient survival was 86, 81 and 74% at 30, 90 and 365 days after graft loss, respectively. About 92% started haemodialysis, 62% with definitive vascular access, which was associated with decreased mortality (hazard ratio = 0.28). At the time of graft loss, most patients were on triple immunosuppressive therapy with significant reduction after nephrectomy. One year after graft loss, 77.5% (31 of 40) of patients in the early and 43.2% (16 out of 37) in the late-loss group had undergone nephrectomy. Three years after graft loss, 36% of the patients with early and 12% with late graft loss received another allograft. CONCLUSION: In summary, our data illustrate high mortality, and a high number of allograft nephrectomies and re-transplantations. Patients commencing haemodialysis with a catheter had significantly higher mortality than patients with definitive access. The role of immunosuppression reduction and allograft nephrectomy as interdependent factors for mortality and re-transplantation needs further evaluation.

Vitamin D deficiency is common in kidney transplant recipients, but is not associated with infections after transplantation.

The relevance of vitamin D for infections after kidney transplantation is poorly defined. 25-OH vitamin D (25-OHD) levels of 135 kidney transplant recipients, enrolled in the Swiss Transplant Cohort Study, were determined peri-transplant and 6 months post-transplant. Logistic regression was used to address the associations of 25-OHD and overall infections and bacterial infections, respectively. For the first 6 months post-transplant, 25-OHD peri-transplant, and for the second period (after 6 to 30 months post-transplant), 25-OHD at 6 months post-transplant was considered. Vitamin D deficiency was common peri-transplant and remained highly prevalent 6 months after transplantation despite frequent supplementation. Median 25-OHD levels increased from 12.0 ng/mL (IQR 5.3-19.5) peri-transplant to 16.5 ng/mL (IQR 10.6-22.6) 6 months post-transplant (P = .005). We did not detect a significant association between 25-OHD and overall infections (adjusted odds ratio (aOR) 1.05, 95% confidence interval (95%CI) 0.44-2.51; aOR 0.67, 95%CI 0.31-1.43) or bacterial infections (aOR 0.79, 95%CI 0.32-1.96; aOR 0.79, 95%CI 0.35-1.75) for the first and second period. To conclude, at both time points, vitamin D deficiency was observed in more than 50% of kidney recipients, albeit an increase in 25-OHD in the longitudinal course was observed. No significant association between 25-OHD and infections was detected.

Effects of hemodialysis on blood volume, macro- and microvascular function.

BACKGROUND: Vascular dysfunction is considered to spur the progression of cardiovascular disease in hemodialysis (HD) patients. Whether the HD procedure itself contributes to vascular dysfunction remains incompletely investigated. The present study sought to comprehensively assess the effects of HD on arterial and venous function along with concomitant changes in blood volume (BV). METHODS AND RESULTS: We determined BV with high-precision, automated carbon monoxide-rebreathing, arterial stiffness using applanation tonometry and intrinsic microvascular function via retinal vessel analysis prior to and after conventional 4-hour HD in fasting-controlled conditions in 10 patients. All HD patients were non-smokers and non-obese (body mass index = 22.8 ±â€¯2.8 m·kg-2). Hypertension (70%), coronary artery disease (40%) and diabetes mellitus (20%) were the most prevalent comorbidities. Prior to HD, all patients presented with hypervolemia (+2208 ±â€¯1213 ml). HD decreased body weight (-1.72 ±â€¯1.25 kg, P = 0.002) and plasma volume (-689 ±â€¯566 ml, P = 0.004), while hematocrit (Hct) was concomitantly increased (+4.8 ±â€¯4.5%, P = 0.009). HD did not affect large elastic artery stiffness, as determined by carotid-femoral pulse wave velocity (P = 0.448) and carotid distensibility (P = 0.562). In contrast, flicker light-induced retinal venular dilation was reduced by three-fourths after HD (-2.4 ±â€¯1.7%, P = 0.039), in parallel to increased retinal venular diameter (+11.2 ±â€¯4.9 µm, P = 0.002). In regression analyses, a negative association was observed between HD-induced changes in Hct and retinal venular dilation (r ≥ -0.89, P ≤ 0.045). CONCLUSION: Conventional HD resulting in substantial plasma volume removal do not alter large artery elastic properties, whereas intrinsic microvascular venular dilator function is markedly impaired, an effect directly associated with the increase in hemoconcentration.

Follow-Up of Bone Mineral Density Changes in de novo Kidney Transplant Recipients Treated with Two Doses of the Receptor Activator of Nuclear Factor κB Ligand Inhibitor Denosumab.

BACKGROUND: Studies in women with post-menopausal osteoporosis have shown that discontinuation of treatment with denosumab leads to an increased risk of vertebral fractures because of rebound bone turnover and rapid loss of bone mineral density (BMD). METHODS: In a post hoc analysis of the Prolia for Osteoporosis of Transplant Operated Patient study, we analyzed the effect of denosumab withdrawal on BMD changes. Twenty-five de novo kidney transplant recipients (KTR) who were treated for 1 year with 2 six-monthly doses of denosumab on top of standard treatment (daily calcium and vitamin D) were compared to a control group of 29 KTR who received standard treatment alone. BMD changes were analyzed by repeated dual-energy X-ray absorptiometry shortly after transplantation (baseline), after 6 and 12 months (active treatment phase) and after 2-6.5 years (follow-up phase). RESULTS: The average BMD at the lumbar spine declined markedly after discontinuation of treatment with denosumab but increased again thereafter. Thus, the average monthly change in lumbar spine BMD from month 12 onward was only 0.1 ± 2.8‰ in the denosumab group but 1.5 ± 1.9‰ in the control group (p = 0.021). The average monthly change in lumbar spine BMD from baseline to follow-up was similar in the control and denosumab group (1.1 ± 1.2‰ vs. 1.5 ± 2.4‰, p = 0.788). Similar results were seen at the total hip. CONCLUSIONS: In de novo KTR treated with 2 doses of denosumab, we detect a marked decrease in lumbar spine and hip BMD when denosumab is discontinued. Denosumab treatment should therefore not be discontinued without considering an alternative antiresorptive treatment.

Relationship of Serum Bicarbonate Levels with 1-Year Graft Function in Kidney Transplant Recipients in Switzerland.

BACKGROUND: Metabolic acidosis (MA) is common in kidney transplant recipients (KTRs). Several studies have shown that MA is involved in the progression of chronic kidney disease. However, it is unclear if there is also a relationship between serum bicarbonate and graft function after kidney transplantation (KTx). We hypothesized that low serum bicarbonate is associated with a lower estimated glomerular filtration rate (eGFR) 1 year after KTx. METHODS: We performed a post hoc analysis of a single-center, open-label randomized trial in 90 KTRs and investigated the relationship of serum bicarbonate and graft function in the first year after KTx. RESULTS: Prevalence of MA was high after KTx (63%) and decreased to 28% after 1 year. Bicarbonate (20.6 ± 3.0 to 22.7 ± 2.7 mmol/L) increased in the first year after transplantation whereas eGFR (53.4 ± 15.8 to 56.9 ± 18.5 mL/min/1.73 m2) did not change significantly. Higher serum bicarbonate (p = 0.029) was associated with higher eGFR in the first year after KTx. CONCLUSION: Prevalence of MA is high in KTRs. In the first year after KTx, serum bicarbonate was positively correlated with eGFR, suggesting a potential role of MA in kidney graft function.

Effect of denosumab on trabecular bone score in de novo kidney transplant recipients.

BACKGROUND: Kidney transplant recipients (KTR) are at risk to lose bone mass. The trabecular bone score (TBS) represents a recently developed parameter of lumbar spine trabecular bone texture that correlates with the occurrence of fractures. METHODS: We analysed the 1-year changes in TBS in 44 de novo KTR that were randomized 1:1 to denosumab or no treatment. TBS was derived from dual energy X-ray absorptiometry and was correlated with 1-year areal bone mineral density (aBMD) changes at the lumbar spine and total hip. Correlations were also performed with parameters of peripheral bone microarchitecture and bone strength at the distal tibia and distal radius, as assessed by high-resolution peripheral quantitative computed tomography (HRpQCT) and micro-finite element analysis. RESULTS: The baseline TBS in KTR amounted to 1.312 ± 0.101, which is lower than the TBS of an age-matched normal control population (range 1.364-1.471). The TBS correlated positively with aBMD at the lumbar spine (Spearman's ρ = 0.56; P < 0.001) and total hip (ρ = 0.33; P < 0.05). The baseline TBS also correlated with HRpQCT-derived total (ρ = 0.49; P < 0.05) and trabecular volumetric BMD (ρ = 0.57; P < 0.01) and trabecular separation (ρ = -0.46; P < 0.05) at the tibia. Denosumab treatment led to an increase in TBS, paralleling the BMD changes at the lumbar spine. CONCLUSIONS: The TBS is a useful additional score of bone health, which may help to better define fracture risk. Treatment with denosumab led to improved trabecular bone texture in de novo KTR in addition to its beneficial effect on BMD.

Bone metabolism dynamics in the early post-transplant period following kidney and liver transplantation.

Bone disease contributes to relevant morbidity after solid organ transplantation. Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends on the endocrine function of both, liver and kidney. Our study assessed key markers of bone metabolism at time of transplantation and 6 months after transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients 25-OH vitamin D levels did not differ significantly between peri-transplant (median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272). Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300% (from 9.1 to 36.5ng/l; P<0.001) and median intact parathyroid hormone levels decreased by 68.4% (from 208.7 to 66.0 ng/l; P<0.001). Median ß-Crosslaps (CTx) and total procollagen type 1 amino-terminal propeptide (P1NP) decreased by 65.1% (from 1.32 to 0.46ng/ml; P<0.001) and 60.6% (from 158.2 to 62.3ng/ml; P<0.001), respectively. Kidney recipients with incident fractures had significantly lower levels of 1, 25-(OH)2 vitamin D at time of transplantation and of intact parathyroid hormone 6 months post-transplant. Among 70 liver recipients, 25-OH vitamin D, 1, 25-(OH)2 vitamin D and intact parathyroid hormone levels were not significantly altered between peri-transplant and 6 months post-transplant. Contrary to kidney recipients, median CTx increased by 60.0% (from 0.45 to 0.72 ng/ml; P = 0.002) and P1NP by 49.3% (from 84.0 to 125.4ng/ml; P = 0.001) in the longitudinal course. Assessed biomarkers didn't differ between liver recipients with and without fractures. To conclude, the assessed panel of biomarkers proved highly dynamic after liver as well as kidney transplantation in the early post-transplant period. After kidney transplantation a significant gain in 1, 25-(OH)2 vitamin D combined with a decline in iPTH, CTx and P1NP, whereas after liver transplantation an increase in CTx and P1NP were characteristic.

Evolution of lung and kidney allograft function in patients receiving kidney after lung transplantation.

Calcineurin inhibitor (CNI) toxicity leads to end-stage renal disease in almost half of long-term survivors after lung transplantation, some of them receiving kidney transplants. Little is known about the outcomes of kidney and lung allograft function following kidney after lung transplantation (KALTPL) in the modern era. We retrospectively analyzed a group of 13 consecutive patients who received a KALTPL with respect to their renal and pulmonary function and immunological evolution over 2 years. We documented a stable evolution of forced expiratory volume in 1 second (FEV1) after KALTPL in most patients as well as an excellent kidney graft during the 2-year follow-up period. In our small cohort, living donations showed a significantly higher estimated glomerular filtration rate compared to deceased donation (75.7 compared to 41.6 mL/min). Patients who received a preemptive KALTPL were more likely to improve their lung function after KALTPL. Four patients developed de novo donor-specific antibodies (DSA) against the kidney graft. There were no DSA against shared antigens from the lung allograft. De novo DSA did not lead to graft loss in any patient. All 13 patients survived the first 24 months after KALTPL.

Long-term follow-up of pulmonary function in Fabry disease: A bi-center observational study.

INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder leading to decreased α-galactosidase A enzyme activity and subsequent abnormal accumulation of glycosphingolipids in various organs. Although histological evidence of lung involvement has been demonstrated, the functional impact of these changes is less clear. MATERIALS AND METHODS: Adult patients with FD who had yearly pulmonary function tests (PFT) at two centers from 1999 thru 2015 were eligible for this observational study. Primary outcome measures were the change in forced expiratory volume in the first second (FEV1) and FEV1/FVC over time. As secondary outcome we investigated sex, smoking, enzyme replacement therapy (ERT), residual enzyme activity, and Mainz Severity Score Index as possible predictors. RESULTS: 95 patients (41% male, 38.2 ± 14.5 years) were included. The overall prevalence of bronchial obstruction (BO, (FEV1/FVC < 70%)) was 46%, with male sex, age and smoking as significant predictors. FEV1 decreased 29 ml per year (95% CI -36, -22 ml, p<0.0001). FEV1 decline was significantly higher in males (p = 0.009) and in patients on ERT (p = 0.004). Conclusion: Pulmonary involvement seems to be a relevant manifestation of Fabry disease, and routine PFTs should therefore be included in the multidisciplinary follow-up of these patients.

Infections in De Novo Kidney Transplant Recipients Treated With the RANKL Inhibitor Denosumab.

BACKGROUND: Infections are a major cause of morbidity and mortality in kidney allograft recipients. In this post hoc analysis of a randomized clinical trial which tested the effect of denosumab on bone mineral density, we assessed the impact of this drug on the incidence and severity of infections in the first year after kidney transplantation. METHODS: In this clinical trial, we randomized 90 de novo kidney transplant recipients shortly after transplantation to either denosumab on top of standard treatment (calcium and vitamin D) (n = 46), or to standard treatment alone (n = 44). Among all adverse events, we analyzed all infections that occurred within the first year after transplantation, and compared their incidence and severity in both groups. RESULTS: Overall, we identified more infections (n = 146) in the denosumab group than in the control group (n = 99). The most common infections were urinary tract infection (cystitis) (34.9% vs 25.2%), cytomegalovirus viremia (17.8% vs 24.2%), flu-like syndrome (11.6% vs 14.1%), polyoma (BK) viremia (8.2% vs 11.1%), and herpes simplex infections (5.5% vs 4.0%). Episodes of urinary tract infection (cystitis) occurred more often in the denosumab than in the control group (51 vs 25 episodes in 24 vs 11 patients, P = 0.008), whereas episodes of transplant pyelonephritis or urosepsis were not more frequent (3 vs 5 episodes). CONCLUSIONS: This post hoc analysis reveals that treatment with denosumab to prevent bone loss in first-year kidney transplant recipients was associated with more frequent episodes of urinary tract infections, whereas other infections occurred with similar frequency in both treatment groups.

Chronic Norovirus Infection as a Risk Factor for Secondary Lactose Maldigestion in Renal Transplant Recipients: A Prospective Parallel Cohort Pilot Study.

BACKGROUND: Chronic norovirus infection is an emerging challenge in the immunocompromised host, in whom it may be asymptomatic or present as chronic diarrhea. The mechanisms of diarrhea in chronic norovirus infection are not well understood, but in analogy to Gardia lamblia and rotavirus infections, secondary lactose maldigestion (LM) might be implicated. METHODS: Adult renal transplant recipients who had symptomatic chronic norovirus infection with diarrhea were asked to participate in this prospective parallel cohort study. Renal transplant recipients with otherwise unexplainable chronic diarrhea but absent infection served as control group. In both groups, a lactose hydrogen breath test and a lactose tolerance test were performed after exclusion of primary LM by a negative lactase gene test. RESULTS: Of approximately 800 patients in the cohort of renal transplant recipients at our institution, 15 subjects were included in the present study. Of these, 7 had chronic symptomatic norovirus infection with diarrhea (noro group), and 8 had diarrhea in the absence of norovirus (control group). Lactose hydrogen breath test and lactose tolerance test were positive in all 7 patients (100%) in the noro group, whereas only 1 (12.5%) of 8 patients in the control group had a positive test. Thus, secondary LM was highly prevalent in the noro compared with the control group with an odds ratio of 75.0 (95% confidence interval, 2.6-2153, P = 0.01). CONCLUSIONS: This is the first report showing a positive association of chronic norovirus infection and secondary LM. Further studies with larger patient numbers and longer follow-up are needed to test a causative relationship between both entities.