Increase in 24-Hour Protein Excretion Immediately After Donation Is Associated With Decreased Functional Recovery in Living Kidney Donors

ObjectivesIn this study, we evaluated the occurrence of proteinuria in living kidney donors during the immediate postdonation period, aiming to determine its clinical significance in renal function recovery.Patients and methodsWe enrolled living kidney donors with predonation protein excretion rate (PER) < 150 mg/24 h. Participants were divided into 2 groups according to immediate postdonation PER (4 days after nephrectomy): non-microproteinuria (non-mPr; PER < 150 mg/24 h), n = 244; and immediate postdonation microproteinuria (ImPr; PER ≥ 150 mg/24 h), n = 605.ResultsEstimated glomerular filtration rate (eGFR) did not differ significantly between groups immediately after nephrectomy but was consistently lower in the ImPr group 1 week to 1 year postdonation (1-year postdonation eGFR: ImPr group, 63.6 ± 12.1 mL/min/1.73 m²; non-mPr group, 68.6 ± 12.3 mL/min/1.73 m²; P = .001). Immediate postdonation microproteinuria was an independent predictor of eGFR at 1 year postdonation (β [standard error] = -2.68 [1.15], 95% confidence interval -4.94 to -0.42, P = .02), along with predonation eGFR, age, and sex. Immediate postdonation microproteinuria was more common in donors who were older or male and occurred in 71.3% of kidney donors, suggesting renal injury in this period.ConclusionsAlthough proteinuria generally resolves, its impact persists and can impair renal function recovery. Donors who are older and male are more likely to undergo immediate hyperfiltration after donation.     

The impact of the donors' and recipients' medical complications on living kidney donors' mental health

A minority of living kidney donors (between 5–25%) have poor psychological outcomes after donation. There is mixed evidence on the influence of medical complications on these outcomes. We examined whether medical complications among donors and recipients predicted changes in donors' mental health (psychological symptoms and well‐being) between predonation and 1 year postdonation. One‐hundred and forty‐five donors completed questionnaires on mental health predonation and 3 and 12 months postdonation. Number of recipient rehospitalizations and donor complications (none; minor; or severe) were obtained from medical records at 3 and 12 months after surgery. Multilevel regression analyses were used to examine the association between medical complications and changes in donors' mental health over time after controlling for sociodemographic characteristics. We found that donor complications (P = 0.003) and recipient rehospitalizations (P = 0.001) predicted an increase in donors' psychological symptoms over time. Recipient rehospitalizations also predicted a decrease in well‐being (P = 0.005) over time; however, this relationship became weaker over time. We conclude that medical complications experienced by either the donor or recipient is a risk factor for deterioration in donors' mental health after living kidney donation. Professionals should monitor donors who experience medical complications and offer additional psychological support when needed.     

Single-Center Long-Term Follow-Up of Kidney Donors in Argentina (Hospital Italiano de Buenos Aires)

Introduction

Living kidney donor (LKD) transplantation is increasing due to organ shortage. Clinical studies have shown that the risk of developing end-stage renal disease (ESRD) in donors is similar to that in the general population. Our goal was to evaluate postdonation renal outcomes assessed by glomerular filtration rate (GFR), proteinuria, and blood pressure.

Blood pressure assessment in haemodialysis patients: Comparison between pre-dialysis blood pressure and ambulatory blood pressure measurement

Aim: Hypertension is common in haemodialysis (HD) patients. Determining the most appropriate method of blood pressure (BP) measurement, representative of target organ damage, is still an issue. BP variations between pre‐ and post‐HD treatment, or between on‐dialysis day and off‐dialysis day, are common. The aim of this study was to examine the possible differences between pre‐HD office BP (OBP) levels, inter‐HD (iHD) or HD day 24 h ambulatory BP measurement (ABPM) with 48 h ABPM, where the latter was considered the gold standard. Methods: 163 HD patients were studied. BP was monitored consecutively for 48 h with a Takeda TM2421 device, then sub‐analysed into two periods of 24 h: HD and iHD day. An average of 12 sessions pre‐HD OBP measurements was determined. Results: OBP significantly overestimates systolic (SBP) and diastolic BP (DBP) when compared with 48 h ABPM. SBP and DBP are significantly higher on iHD day than on HD day: 141.2 ± 20.8 versus 137.9 ± 20.9, and 77.1 ± 11.1 versus 76.1 ± 10.9 (P < 0.01). No differences of SBP night/day ratio were reported between 48 h ABPM and iHD 24 h ABPM or HD 24 h ABPM. The highest correlations were reported between 48 h SBP/DBP with iHD or HD 24 h ABPM (r² = 0.95, P < 0.001), while the lowest between 48 h SBP/DBP and OBP (r² = 0.40, P < 0.01, r² = 0.12, P < 0.01). The narrowest limits of agreement using the Bland and Altman test were reported between 48 h SBP or DBP and 24 h iHD or HD day ABPM. Considering 48 h ABPM, 80.5% of patients had BP higher than the norm, compared with 61.7% of patients in the case of OBP (χ² = 13.28, P < 0.001). The sensibility for detecting hypertension for iHD day 24 h ABPM was 98.4%, with specificity of 90%. The sensibility of 24 h HD day ABPM was 90.3%, with specificity 96.6%. In the case of OBP, sensibility and specificity were considerably lower, that is, 72.6% and 83.3% respectively. Conclusion: Significant differences are shown between OBP and 48 h ABPM in the recognition of a hypertensive state. OBP measurement has a lower sensibility and specificity than 24 h ABPM, which remains a valid alternative approach to 48 h ABPM in HD patients. Errors of OBP estimation should be taken into account, with possible negative impact on treatment strategies and epidemiology studies.     

Improvement of Intradialytic Hypotension in Diabetic Hemodialysis Patients Using Vitamin E‐Bonded Polysulfone Membrane Dialyzers

Currently, there are no detailed reports on the effects of vitamin E‐bonded polysulfone (PS) membrane dialyzers on intradialytic hypotension (IDH) in diabetic hemodialysis (HD) patients. This study was designed to evaluate changes in intradialytic systolic blood pressure (SBP) using “VPS‐HA” vitamin E‐bonded super high‐flux PS membrane dialyzers. The subjects were 62 diabetic HD patients whose intradialytic SBP fell by more than 20%. Group A comprised patients who required vasopressors to be able to continue treatment or who had to discontinue therapy due to their lowest intradialytic SBP being observed at 210 min (28 patients). Group B comprised patients who showed no symptoms and required no vasopressors but showed a gradual reduction in blood pressure, with the lowest intradialytic SBP seen at the end of dialysis (34 patients). The primary outcome was defined as the lowest intradialytic SBP after 3 months using VPS‐HA. Secondary outcomes included changes in the following: lowest intradialytic diastolic blood pressure, pulse pressure, pulse rate, plasma nitric oxide and peroxynitrite, serum albumin, and hemoglobin A1c. Group A's lowest intradialytic SBP had significantly improved at 3 months (128.0 ± 25.1 mm Hg vs. 117.1 ± 29.2 mm Hg; P = 0.017). Group B's lowest intradialytic SBP had significantly improved at 1 month (134.4 ± 13.2 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.047) and 3 months (139.1 ± 20.9 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.011). We conclude that VPS‐HA may improve IDH in diabetic HD patients.     

Patterns and predictors of fatigue following living donor nephrectomy: Findings from the KDOC Study

This study sought to identify the prevalence, pattern, and predictors of clinical fatigue in 193 living kidney donors (LKDs) and 20 healthy controls (HCs) assessed at predonation and 1, 6, 12, and 24 months postdonation. Relative to HCs, LKDs had significantly higher fatigue severity (P = .01), interference (P = .03), frequency (P = .002), and intensity (P = .01), and lower vitality (P < .001), at 1‐month postdonation. Using published criteria, significantly more LKDs experienced clinical fatigue at 1 month postdonation, compared to HCs, on both the Fatigue Symptom Inventory (60% vs. 37%, P < .001) and SF‐36 Vitality scale (67% vs. 16%, P < .001). No differences in fatigue scores or clinical prevalence were observed at other time points. Nearly half (47%) reported persistent clinical fatigue from 1 to 6 months postdonation. Multivariable analyses demonstrated that LKDs presenting for evaluation with a history of affective disorder and low vitality, those with clinical mood disturbance and anxiety about future kidney failure after donation, and those with less physical activity engagement were at highest risk for persistent clinical fatigue 6 months postdonation. Findings confirm inclusion of fatigue risk in existing OPTN informed consent requirements, have important clinical implications in the care of LKDs, and underscore the need for further scientific examination in this population.     

Kidney outcomes in patients with liver cirrhosis and chronic kidney disease receiving an orthotopic liver transplant alone

Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney disease (CKD) is controversial. We report 14 liver cirrhotic patients who had persistently low MDRD‐6 estimated glomerular filtration rate (e‐GFR) <40 mL/min/1.73 m² for ≥3 months and underwent either liver transplant alone (LTA; n=9) or simultaneous liver‐kidney transplant (SLKT; n=5). Pretransplant, patients with LTA compared with SLKT had lower serum creatinine (2.5±0.73 vs 4.6±0.52 mg/dL, P=.001), higher MDRD‐6 e‐GFR (21.0±7.2 vs 10.3±2.0 mL/min/1.73 m², P=.002), higher 24‐hour urine creatinine clearance (34.2±8.8 vs 18.0±2.2 mL/min, P=.002), lower proteinuria (133.2±117.7 vs 663±268.2 mg/24 h, P=.0002), and relatively normal kidney biopsy and ultrasound findings. Post‐LTA, the e‐GFR (mL/min/1.73 m²) increased in all nine patients, with mean e‐GFR at 1 month (49.8±8.4), 3 months (49.6±8.7), 6 months (49.8±8.1), 12 months (47.6±9.2), 24 months (47.9±9.1), and 36 months (45.1±7.3) significantly higher compared to pre‐LTA e‐GFR (P≤.005 at all time points). One patient developed end‐stage renal disease 9 years post‐LTA and another patient expired 7 years post‐LTA. The low e‐GFR alone in the absence of other markers or risk factors of CKD should not be an absolute criterion for SLKT in patients with liver cirrhosis.     

Oxidative DNA Damage Is Increased in Living Kidney Donors

BackgroundLong-term consequences of donor nephrectomy might be reduced kidney function, increased risk for cardiovascular disease, and impaired quality of life. The purpose of the current cross-sectional study was to evaluate the relationship between clinical, laboratory, and donation-specific outcomes of living kidney donors and systemic oxidative DNA damage.MethodsWe conducted a cross-sectional study and assessed retrospectively pre- and postdonation data from 60 donors who donated between 2010 and 2015. Plasma malondialdehyde levels and 8-hydroxy-2′-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) were determined as oxidative stress markers. Catalase, carbonic anhydrase, and paraoxonase (PON) activities were measured as antioxidants.ResultsApproximately 3 years after donation, the hypertensive donor ratio was 12%, and 11% of the donors had glomerular filtration rate <60 mL/min/1.73 m². Mean serum urea (P = .001) and serum creatinine levels (P = .001) were increased; creatinine clearance level (126.2 ± 35.5 vs 94.6 ± 26.8, P = .001) was decreased in the postdonation period. There was a significant positive correlation between predonation serum urea and 8-0HdG/dG ratio (r = 0.338, P = .016) and predonation serum creatinine and 8-0HdG/dG ratio (r = 0.442, P = .001), while there was a significant negative correlation between serum creatinine and PON activity (r = ?0.545, P < .001).ConclusionOur data have demonstrated that kidney donors exhibit increased oxidative DNA damage and decreased antioxidant activity. We propose that predonation serum creatinine is positively correlated with 8-0HdG/dG ratio and negatively correlated with antioxidant PON activity. This is the first study to demonstrate that plasma oxidative DNA damage increases in healthy kidney donors.     

Cystatin C: influence of perfusion and myocardial injury on early (<24 h) renal function after pediatric cardiac surgery

Background: Cardiopulmonary bypass (CPB)‐associated renal dysfunction following cardiac surgery is well recognized. In patients with renal disease, cystatin C has emerged as a new biomarker which in contrast to creatinine (Cr) is sensitive to minor changes in glomerular filtration rate (GFR). Aim: We utilized cystatin C to investigate the association of CPB perfusion parameters with acute renal injury after pediatric cardiac surgery. Methods: Twenty children, aged 4–58 months (AVSD, n = 7; VSD, n = 9; and ASD, n = 4), were prospectively studied. Glomerular filtration rate was quantified postoperatively by creatinine clearance (first and second 12‐h periods; CrCl_0–12 and CrCl_12–24). Serum cystatin C and Cr were measured preoperatively and on days 0–3. Recorded CPB parameters included bypass duration (BP), perfusion pressure (PP), lowest pump flow (Q_min), lowest hematocrit, and corresponding lowest oxygen delivery (DO_{2 min}). Myocardial injury was determined by troponin‐I. Results: Postoperatively, GFR remained unchanged (CrCl_0–12 63.6 ± 37.0 vs CrCl_12–24 65.1 ± 27.5; P = 0.51) and only correlated with cystatin C (CrCl_0–12 vs cystatin C_Day0 [r = 0.58, P = 0.018] and Cr_Day0 [r = 0.09, P = 0.735]). Cr and cystatin C increased postoperatively to peak on days 2 and 3, respectively (Cr_PreOp 31 ± 6.9 vs Cr_Day2 36.9 ± 12.2, P = 0.03; cystatin C_Day0 0.83 ± 0.27 vs cystatin C_Day3 1.45 ± 0.53, P = 0.02). Increased cystatin C was significantly associated with BP (P = 0.001), mean PP (P = 0.029), Q_min (P = 0.005), troponin‐I (P < 0.001), and DO_2min <300 ml·min^?1·m^?2 (P = 0.007). Receiver–operator cutoff >1.044 mg·l^?1 for cystatin C exhibited 100% sensitivity and 67% specificity for detecting renal dysfunction, defined as GFR <55 ml·min^?1·1.73 m^?2. Conclusions: Cystatin C is a sensitive marker of early renal dysfunction following pediatric heart surgery. Variations in bypass parameters, myocardial injury, and ultimately critical oxygen delivery are significantly associated with the degree of renal impairment.     

Association between interleukin-10 gene polymorphism -592 (A/C) and peritoneal transport in patients undergoing peritoneal dialysis

Aim: The aim of this analysis was to know whether these three cytokine polymorphisms, including interleukin‐6 (IL‐6; ?572 G/C), tumour necrosis factor‐α (TNF‐α; ?308 G/A), and IL‐10 (–592 A/C) have an effect on baseline peritoneal transport property and longitudinal evolution of peritoneal function. Methods: A total of 141 stable peritoneal dialysis (PD) patients with mean treatment duration of 84.4 ± 34.2 months were enrolled. We genotyped these three cytokine polymorphisms, together with clinical parameters that were included as factors affecting longitudinal change of property of peritoneal transport over the first 3 year period after commencing therapy. Results: There was no significant association between genotypes and baseline peritoneal transport property. The ?592 A/C polymorphism of IL‐10 was associated with longitudinal change of peritoneal transport. The ratio of D/P creatinine was significantly higher in patients with AA than those with CC/CA genotypes at 12 months (0.65 ± 0.11 vs 0.62 ± 0.09, P = 0.048) and 24 months (0.64 ± 0.12 vs 0.59 ± 0.09, P = 0.018). In addition, patients with increased peritoneal transport have greater frequency distribution of AA genotype and A allele. Logistic regression analysis revealed that ?592 A allele was an independent predictor for the increase in D/P creatinine over the first 12 month period (odds ratio: 2.482, P = 0.017). There was no correlation between either polymorphism of IL‐6 ?572 (G/C) or TNF‐α?308 (G/A) and longitudinal change of peritoneal function. Conclusions: Single nucleotide polymorphism of IL‐10 ?592 (A/C) was associated with longitudinal evolution of peritoneal transport rate in PD patients rather than the baseline peritoneal characteristics.     

Bridging a 30 mm defect in the canine ulnar nerve using vessel‐containing conduits with implantation of bone marrow stromal cells

Previously, we showed that undifferentiated bone marrow stromal cell (uBMSC) implantation and vessel insertion into a nerve conduit facilitated peripheral nerve regeneration in a rodent model. In this study, we investigated the efficacy of the uBMSC‐laden vessel‐containing conduit in repair of segmental nerve defects, using a canine model. Eight beagle dogs were used in this study. Thirty‐millimeter ulnar nerve defects were repaired with the conduits (right forelimbs, n = 8) or autografts (left forelimbs, n = 7). In the conduit group, the ulnar artery was inserted into the l‐lactide/ε‐caprolactone tube, which was filled with autologous uBMSCs obtained from the ilium. In the autograft group, the reversed nerve segments were sutured in situ. At 8 weeks, one dog with only nerve repair with the conduit was sacrificed and the regenerated nerve in the conduit underwent immunohistochemistry for investigation of the differentiation capability of the implanted uBMSCs. In the remaining seven dogs, the repaired nerves underwent electrophysiological examination at 12 and 24 weeks and morphometric measurements at 24 weeks. The wet weight of hypothenar muscles was measured at 24 weeks. At 8 weeks, almost 35% of the implanted uBMSCs expressed glial markers. At 12 weeks, amplitude (0.4 ± 0.4mV) and conduction velocity (18.9 ± 14.3m/s) were significantly lower in the conduit group than in the autograft group (3.2 ± 2.5 mV, 34.9 ± 12.1 m/s, P < 0.05). Although the nerve regeneration in the conduit group was inferior when compared with the autograft group at 24 weeks, there were no significant differences between both groups, regarding amplitude (10.9 ± 7.3 vs. 25.3 ± 20.1 mV; P = 0.11), conduction velocity (23.5 ± 8.7 vs 31.6 ± 20.0m/s; P = 0.35), myelinated axon number (7032 ± 4188 vs 7165 ± 1814; P = 0.94), diameter (1.73 ± 0.31 vs 2.09 ± 0.39μm; P = 0.09), or muscle weight (1.02 ± 0.40 vs 1.19 ± 0.26g; P = 0.36). In conclusion, this study showed that vessel‐containing tubes with uBMSC implantation may be an option for treatment of peripheral nerve injuries. However, further investigations are needed. © 2015 Wiley Periodicals, Inc. Microsurgery 36:316–324, 2016.     

Irbesartan promotes erection recovery after nerve‐sparing radical retropubic prostatectomy: a retrospective long‐term analysis

Study Type – Therapy (retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Erectile dysfunction following radical prostatectomy (RP) is among the most common and dreaded adverse effects of the surgery. Multiple studies confirm the potential benefit of various drug classes to accelerate the return of erectile function (EF) after RP. There is pre‐clinical evidence supporting the use of angiotensin‐receptor blockers (ARBs) for this purpose, although this has not been studied in humans. The present study shows that there may be a benefit in the recovery of EF post‐RRP in patients taking a daily dose of irbesartan, an ARB, following RRP. In addition, the use of irbesartan may curb the loss of stretched penile length which occurs postoperatively. Further study in the form of prospective, randomized, placebo‐controlled clinical trials are necessary to confirm these findings.

OBJECTIVE

• ? To evaluate retrospectively the potential benefit of administering irbesartan, an angiotensin‐receptor blocker, to improve erectile function (EF) recovery after nerve‐sparing radical retropubic prostatectomy (RRP).

PATIENTS AND METHODS

• ? Before surgery potent patients who underwent nerve‐sparing RRP between April and December 2009 elected to start daily oral irbesartan 300 mg on postoperative day 1 (n= 17). A contemporaneously clinically matched cohort consisting of patients who declined irbesartan use served as the control group (n= 12).
• ? Postoperative ‘on demand’ use of erectile aids (phosphodiesterase type 5 [PDE5] inhibitors and intracavernous injections) was adopted.
• ? Potency was monitored by the administration of International Index of Erectile Function‐5 (IIEF‐5) questionnaires before surgery and at early (3 months) and long‐term (12 and 24 months) postoperative intervals.
• ? Stretched penile length (SPL) was measured both immediately and 3 months after surgery.

RESULTS

• ? EF status was no different between groups at baseline (P > 0.05).
• ? While the IIEF‐5 scores at 24 months after surgery were statistically similar between the two groups (control = 15.2 ± 2.0, irbesartan = 14.1 ± 3.1, P= 0.77), at 12 months the IIEF‐5 scores of the irbesartan group were significantly higher than those of the control group (14 ± 2.6 vs. 7.2 ± 1.6, P < 0.05).
• ? The proportional loss of SPL after RRP was less in the irbesartan than in the control group at 3 months (–0.9 ± 1.5% vs –5.6 ± 1.5, P < 0.05).

CONCLUSION

• ? Regular irbesartan use after nerve‐sparing RRP in patients with normal preoperative erectile function could improve EF recovery after surgery and mitigate early loss of SPL.

     

Renal volume assessed by magnetic resonance imaging volumetry correlates with renal function in living kidney donors pre‐ and postdonation: a retrospective cohort study

Renal function of potential living kidney donors is routinely assessed with scintigraphy. Kidney anatomy is evaluated by imaging techniques such as magnetic resonance imaging (MRI). We evaluated if a MRI‐based renal volumetry is a good predictor of kidney function pre‐ and postdonation. We retrospectively analyzed the renal volume (RV) in a MRI of 100 living kidney donors. RV was correlated with the tubular excretion rate (TER) of MAG3‐scintigraphy, a measured creatinine clearance (CrCl), and the estimated glomerular filtration rate (eGFR) by Cockcroft‐Gault (CG), CKD‐EPI, and modification of diet in renal disease (MDRD) formula pre‐ and postdonation during a follow‐up of 3 years. RV correlated significantly with the TER (total: r = 0.6735, P < 0.0001). Correlation between RV and renal function was the highest for eGFR by CG (r = 0.5595, P < 0.0001), in comparison with CrCl, MDRD‐GFR, and CKD‐EPI‐GFR predonation. RV significantly correlated with CG‐GFR postdonation and predicted CG‐GFR until 3 years after donation. MRI renal volumetry might be an alternative technique for the evaluation of split renal function and prediction of renal function postdonation in living kidney donors.     

Postdonation Anemia in Living Kidney Donors

Background

The effect of nephrectomy on development of anemia in living kidney donation has not been well studied. We hypothesized that the remaining kidney volume and function after donation are determinants of hemoglobin (Hb) concentration and postdonation anemia (PDA).

Pre‐ and postdonation kidney function in donors of a kidney paired donation with unique criteria for donor glomerular filtration rate – a longitudinal cohort analysis

Baseline predonation estimated GFR (eGFR) appears to predict the risk of postdonation chronic kidney disease in live donors. New KIDGO guidelines recommend an eGFR ≥90 ml/min/1.73 m² as an acceptable level of glomerular filtration rate (GFR) for kidney donation. In the Australian Paired Kidney Exchange (AKX) program, all donors with a raw measured GFR (mGFR) ≥80 ml/min are deemed suitable for donation, but the significance of this selection indicator is unclear. We analysed the first 129 live donors in the AKX program with at least 1‐year follow‐up linking records in the AKX database and ANZDATA. There were 73 male and 56 female donors; mean (±SD) age was 53 ± 11 years. Predonation eGFR was 94 ± 13 ml/min/1.73 m², mGFR 99 ± 17 ml/min/1.73 m² and raw mGFR 108 ± 18 ml/min. Baseline eGFR was <80 ml/min/1.73 m² in 19 donors, and <90 ml/min/1.73 m² in 42 donors. At 1 year postdonation eGFR was 68 ± 15 ml/min/1.73 m² and the predicted eGFR at 30 years postdonation was on average 50 (29–83) ml/min/1.73 m². The hypothetical mean age at end‐stage kidney disease was estimated to be 145 (95% CI 120–263) years. Over 30% of AKX live donors would have been excluded from donation using KDIGO guidelines. Using AKX donor guidelines, the majority of donors with predicted eGFR <30 ml/min/1.73 m² 30‐year postdonation were aged ≥50 years. Long‐term outcome data on AKX donors with low eGFR will need careful monitoring.     

Impact of anti‐HCV direct antiviral agents on graft function and immunosuppressive drug levels in kidney transplant recipients: a call to attention in the mid‐term follow‐up in a single‐center cohort study

The medium‐term impact on graft function and immunosuppressive drug pharmacokinetics of direct antiviral agents (DAA s) among hepatitis C virus (HCV )‐infected kidney transplant (KT ) recipients remain unclear. We compared pre‐ and post‐treatment 12‐month trajectories of estimated glomerular filtration rate (ΔeGFR ) and 24‐h proteinuria (Δ24‐h proteinuria) in 49 recipients treated with DAA s (mostly sofosbuvir plus ledipasvir). Among evaluable patients, 66.7% and 100.0% had undetectable viral load by week 4 and end of therapy (EoT). The sustained virologic response rate at 12 weeks was 95.8%. Overall, 80.6% of patients receiving tacrolimus required dose escalation while on DAA ‐based therapy (median increase of 66.7%) to maintain target levels. Tacrolimus levels resulted to be higher at 12 months compared to EoT (7.8 ± 2.1 vs. 6.7 ± 2.0 ng/ml ; P ‐value = 0.002). No changes in graft function during the course of therapy were observed. However, eGFR significantly decreased (P ‐value <0.001) throughout the first 12 months after EoT. Median ΔeGFR and Δ24‐h over pre‐ and post‐treatment periods were 3.9% and ?6.1% (P ‐value = 0.002) and ?5.3% and 26.2% (P ‐value = 0.057). Caution should be exercised when adjusting immunosuppression in HCV ‐infected KT recipients upon initiation of DAA s, followed by mid‐term monitoring of immunosuppressive drug levels and graft function.     

Five‐year follow‐up after live donor nephrectomy – cross‐sectional and longitudinal analysis of a prospective cohort within the era of extended donor eligibility criteria

To establish the outcome of live kidney donors 5 years after donation, we investigated the risk for progressive renal function decline and quality of life (QoL). Data on estimated glomerular filtration rate (eGFR), creatinine, hypertension, QoL and survival were assessed in a prospective cohort of 190 donors, who donated between 2008 and 2010. Data were available for >90%. The mean age predonation was 52.8 ± 11.5 years, 30 donors having pre‐existent hypertension. The mean follow‐up was 5.1 ± 0.9 years. Eight donors had died due to non‐donation‐related causes. After 5 years, the mean eGFR was 60.2 (95% CI 58.7–62.7) ml/min/1.73 m², with a median serum creatinine of 105.1 (95% CI 102.5–107.8) μmol/l. eGFR decreased to 33.6% and was longitudinally lower among men than women and declining with age (P < 0.001), without any association on QoL. Donors with pre‐existent and new‐onset hypertension demonstrated no progressive decline of renal function overtime compared to nonhypertensives. No donors were found with proteinuria, microalbuminuria or at risk for end‐stage renal disease. After an initial decline postdonation, renal function remained unchanged overtime. Men and ageing seem to affect renal function overtime, while decreased renal function did not affect QoL. These data support further stimulation of living kidney donation programmes as seen from the perspective of donor safety.     

Effect of everolimus vs calcineurin inhibitors on quality of life in heart transplant recipients during a 3‐year follow‐up: Results of a randomized controlled trial (SCHEDULE)

The Sc andinavian he art transplant everolimus d e novo st u dy with ear l y calcineurin inhibitors avoidanc e (SCHEDULE) trial was a 12 month, randomized, open‐label, parallel‐group trial that compared everolimus (EVR; n=56) to conventional CsA (n=59) immunosuppression. Previously, we reported that EVR outperformed CsA in improving renal function and coronary artery vasculopathy, despite a higher rejection rate with EVR. This study aimed to compare the effects of these treatments on quality of life (QoL). Within five post‐operative days, patients (mean age 50±13 years, 27% women) were randomized to EVR or a standard CsA dosage (CsA group). This study assessed quality of life (QoL), based on the Short Form‐36, EuroQol‐5D, and Beck Depression Inventory (BDI). Assessments were performed pre‐HTx and 12 and 36 months post‐HTx. At 12 and 36 months, the groups showed similar improvements in Short Form‐36 measures (at pre‐HTx, 12 and 36 months the values were as follows: Physical component summary: EVR: 31.5±110.9, 49.1±9.7, and 47.9±10.6; P<.01; CsA: 32.5±8.2, 48.4±8.5, and 46.5±11.5; P<.01; mental component summary: EVR: 46.0±12.0, 51.7±11.9, and 52.1±13.0; P<.01; CsA: 38.2±12.5, 53.4±7.1, and 54.3±13.0; P<.01); similar decrease in mean BDI (EVR: 10.9±10.2, 5.4±4.7, and 8.1±9.0; P<.01; CsA: 11.8±7.1, 6.3±5.4, and 6.2±6.5; P<.01); and similar Euro Qol‐improvements. Thus, in this small‐sized study, EVR‐based and conventional CsA immunosuppressive strategies produced similar QoL improvements.     

Pancreatico‐jejunostomy decreases post‐operative pancreatic fistula incidence and severity after central pancreatectomy

Backgrounds

Central pancreatectomy (CP) is an alternative to pancreaticoduodenectomy and distal pancreatectomy in benign tumours of pancreatic isthmus management. It is known for a high post‐operative pancreatic fistula (POPF) rate. The purpose of this study was to compare POPF incidence between pancreatico‐jejunostomy (PJ) and pancreatico‐gastrostomy (PG).

Methods

Fifty‐eight patients (mean age 53.9 ± 1.9 years) who underwent a CP in four French University Hospitals from 1988 to 2011 were analysed. The distal pancreatic remnant was either anastomosed to the stomach (44.8%, n = 25) or to a Roux‐en‐Y jejunal loop (55.2%, n = 35) with routine external drainage allowing a systematic search for POPF. POPF severity was classified according to the International Study Group on Pancreatic Fistula (ISGPF) and Clavien‐Dindo classifications.

Results

The groups were similar on sex ratio, mean age, ASA score, pancreas texture, operative time and operative blood loss. Mean follow‐up was 36.2 ± 3.9 months. POPF were significantly more frequent after PG (76.9 versus 37.5%, P = 0.003). PG was associated with significantly higher grade of POPF both when graded with ISGPF classification (P = 0.012) and Clavien‐Dindo classification (P = 0.044). There was no significant difference in post‐operative bleeding (0.918) and delayed gastric emptying (0.877) between the two groups. Hospital length of stay was increased after PG (23.6 ± 3.5 days versus 16.5 ± 1.9 days, P = 0.071). There was no significant difference in incidence of long‐term exocrine (3.8 versus 19.2%, P = 0.134) and endocrine (7.7 versus 9.4%, P = 0.575) pancreatic insufficiencies.

Conclusion

PG was associated with a significantly higher POPF incidence and severity in CP. We recommend performing PJ especially in older patients to improve CP outcomes.     

Efficacy of extended‐release tolterodine for the treatment of neurogenic detrusor overactivity and/or low‐compliance bladder

Objective: To evaluate the efficacy of extended‐release (ER) tolterodine 4 mg/day for the treatment of neurogenic detrusor overactivity (NDO) and/or low‐compliance bladder by assessing urodynamic parameters. Methods: Forty‐six patients (25 male, 21 female; mean age 57.6 ± 20.7 years) with NDO (n = 39) and/or low‐compliance bladder (n = 7) were included in this 12‐week single‐arm study. Twenty‐one patients (46%) were on clean intermittent catheterization and other patients could void on their own. A video urodynamic study was performed before and at 3 months after treatment. Changes in Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Questionnaire–Short Form (ICIQ‐SF), and King's Health Questionnaire (KHQ) as well as changes in number of voids, amount of each void, and number of leaks in 24 h according to the 3‐day voiding diary were also evaluated before treatment and at weeks 4 and 12 after treatment. Results: Bladder capacity at first sensation and maximum cystometric capacity increased significantly, by an average of 36.8 mL (P = 0.0402) and 82.3 mL (P < 0.0001), respectively. Maximum cystometric capacity increased by more than 50 mL in 19 patients (49%) following treatment. Detrusor overactivity disappeared in three of 32 patients (9%), bladder capacity at first involuntary contraction increased significantly (P = 0.0009), and amplitude of detrusor overactivity decreased significantly (P = 0.0025). In patients with low‐compliance bladder, bladder compliance increased significantly (P = 0.0156). Overactive bladder symptom score, International Consultation on Incontinence Questionnaire–Short Form score, number of voids (per 24 h and night‐time), number of urgency episodes in 24 h, number and amount of leaks in 24 h, and amount of mean and maximum voided volumes all decreased significantly after treatment. Conclusion: Tolterodine is effective and well tolerated for the treatment of NDO and/or low‐compliance bladder in patients with neurogenic bladder.