Patients undergoing double J substitution with a pigtail suture stent report a significant decrease of stent-related symptoms. Results from a prospective multicenter longitudinal trial.

PURPOSE: To compare stent-related symptoms (SRS) in patients with double J (DJ) undergoing substitution with a pigtail suture stent (PSS) after ureteroscopy (URS), through the Ureteral Stent Symptom Questionnaire (USSQ). MATERIALS AND METHODS: Patients with DJ undergoing URS for stone treatment were enrolled in this prospective multicenter longitudinal study. The USSQ was submitted thrice: 2 weeks after DJ, 2 weeks after PSS and 4 weeks after PSS removal (baseline). PRIMARY ENDPOINT: to compare Urinary Symptom Index Score and the rate of patients with pain 2 weeks after DJ and PSS. Secondary endpoints: to compare other USSQ scores and single answers 2 weeks after DJ and PSS, and DJ and PSS USSQ scores with baseline. RESULTS: 93 patients were enrolled. 2 weeks Urinary Symptom Index Score (p < 0.001) and the percentage of patients complaining of pain (60.2% vs 88.2%, p < 0.001) were significantly in favour of PSS compared to DJ. 2 weeks scores were significantly improved with PSS compared to DJ: Pain Index (p < 0.001), VAS (p < 0.001), General Health Index (p < 0.001) and Work Performance Index (p < 0.001). All urinary symptoms were significantly decreased with PSS, including renal pain during micturition and pain interfering with life. Pain Index Score (p = 0.622) and VAS (p = 0.169) were comparable to baseline with PSS, while differed with DJ. CONCLUSIONS: Patients undergoing DJ substitution with PSS after URS report a significant decrease of SRS. Urologists may consider positioning PSS after URS in pre-stented patients to reduce the impact of SRS.

Significant Long-Term Prevention of High Sensitization After Kidney Allograft Failure by Maintaining Calcineurin Inhibitor-Based Immunosuppression.

INTRODUCTION: Broad national or international programs contribute to mitigating the expected longer waiting list (WL) time for sensitized patients but with minor benefits for highly sensitized subjects. Therefore, strategies to prevent high sensitization are urgently required. In this study, we investigated the risk of developing highly sensitized patients with different immunosuppressive (IS) handling after kidney allograft failure (KAF). METHODS: Data from 185 patients with KAF, retransplanted/relisted from 2010 to 2020 in two regions of Italy that share the same regional WL, were analyzed. Patients were categorized according to IS management at 12 months after KAF as follows: patients maintaining IS with calcineurin inhibitors (CNI) (late withdrawal group [LWG], n = 58) and those who withdrew all IS therapy or were on steroids only (early withdrawal group [EWG], n = 127). RESULTS: Patients in the LWG showed lower panel reactive antibodies (PRA) at 12 (29.0% vs. 85.5%, p < 0.001) and 24 months (61.0% vs. 91.0%, p = 0.001), reduced risk of high sensitization (PRA ≥90%) at 12 (9.4% vs. 40.7%, p < 0.001, OR = 0.15) and 24 months (25.6% vs. 57.3%, p = 0.001, OR = 0.26) and almost no very high sensitization (PRA ≥ 98%) at 12 months (1.9% vs. 18.6%, p = 0.003, OR = 0.08) after KAF. In the LWG subgroup analysis, patients who maintained IS for up to 24 months after KAF did not show very high sensitization. The LWG showed shorter active WL times (406 vs. 813 days, p = 0.001) without an increased risk of complications. CONCLUSIONS: CNI maintenance for at least 12 months after KAF could be a useful approach to prevent high sensitization and reduce WL times in patients who are offered retransplantation, without a higher burden of complications.

Loop-tail stents fail in reducing stent-related symptoms: results of a prospective randomised controlled trial.

OBJECTIVE: To compare stent-related symptoms (SRS) of loop-tail (LT) and conventional double J (DJ) stents after uncomplicated flexible ureterorenoscopy (fURS), in a prospective randomised controlled single-blind parallel-group study. PATIENTS AND METHODS: Patients undergoing fURS were randomised into two groups: the LT Group received LT stents (Polaris™ Loop) and the DJ Group received conventional DJ stents (Vortek® ). The stent was removed after 4 weeks. The Ureteric Stent Symptom Questionnaire (USSQ) was administered at 2 days, 4 and 8 weeks (baseline evaluation) after stent insertion. The primary endpoint was to compare the Urinary Symptom Index Score of the LT vs DJ groups at 4 weeks after stent insertion. The secondary endpoints were to compare the USSQ domains' subscores at 2 days and 4 weeks after stent insertion, USSQ single answers at 4 weeks, and the 4-week USSQ domains' subscores adjusted for baseline. RESULTS: A total of 68 patients were randomised (34 LT and 34 DJ). The answers given at 4 weeks were not significantly different between the two groups for the Urinary Symptom Index Score (P = 0.982), Pain Index Score (P = 0.169), visual analogue scale (P = 0.276), and all the other domains of the USSQ. At 4 weeks, the single-answer analysis did not find any differences between the groups; the urinary symptoms were all comparable, as was the requirement for pain painkillers (P = 0.684) and pain during sex (P = 0.496). There were also no significant differences for every single domain score for the responses given at 2 days. The same applied to USSQ subscores at 4 weeks adjusted for the 8-week baseline results, which were also comparable. CONCLUSIONS: The study found no differences in terms of SRS between the LT and DJ groups, either at 2 days or 4 weeks after stent insertion, with or without baseline correction.

Clinical outcomes and temporal trends of immunological and non-immunological rare diseases in adult kidney transplant.

BACKGROUND: Rare diseases (RDs) encompass many difficult-to-treat conditions with different characteristics often associated with end-stage renal disease (ESRD). However, data about transplant outcomes in adult patients are still lacking and limited to case reports/case series without differentiation between immunological/non-immunological RDs. METHODS: Retrospective analysis among all adult kidney transplanted patients (KTs) with RDs (RDsKT group) performed in our high-volume transplantation center between 2005 and 2016. RDs were classified according to the Orphanet code system differentiating between immunological and non-immunological diseases, also comparing clinical outcomes and temporal trends to a control population without RDs (nRDsKT). RESULTS: Among 1381 KTs, 350 patients (25.3%) were affected by RDs (RDsKTs). During a f/up > 5 years [median 7.9 years (4.8-11.1)], kidney function and graft/patient survival did not differ from nRDsKTs. Considering all post-transplant complications, RDsKTs (including, by definition, patients with primary glomerulopathy except on IgA nephropathy) have more recurrent and de-novo glomerulonephritis (14.6% vs. 9.6% in nRDsKTs; p = 0.05), similar rates of de-novo cancers, post-transplant diabetes, dysmetabolism, hematologic disorders, urologic/vascular problems, and lower infectious episodes than nRDsKTs (63.7% vs 72.7%; p = 0.013). Additional stratification for immunological and non-immunological RDsKTs or transplantation periods (before/after 2010) showed no differences or temporal trends between groups. CONCLUSIONS: Kidney transplant centers are deeply involved in RDs management. Despite their high-complex profile, both immunological and non-immunological RDsKTs experienced favorable patients' and graft survival.

Acute and chronic glomerular damage is associated with reduced CD133 expression in urinary extracellular vesicles.

Extracellular vesicles released into urine (uEVs) can represent interesting biomarkers of renal cell damage. CD133, a stem/progenitor cell marker expressed by renal progenitor cells, is highly expressed in uEVs of healthy individuals. In the present study, we evaluated the level of CD133 in the uEVs of patients with acute and chronic glomerular damage by cytofluorimetric analysis. The level of CD133+ uEVs was significantly decreased in pediatric patients with acute glomerulonephritis during the acute phase of renal damage, while it was restored after the subsequent recovery. A similar decrease was also observed in patients with chronic glomerulonephritis. Moreover, CD133+ uEVs significantly declined in patients with type 2 diabetes, used as validation group, with the lowest levels in patients with albuminuria with diabetic nephropathy. Indeed, receiver-operating characteristic curve analysis indicates the ability of CD133+ uEV values to discriminate the health condition from that of glomerular disease. In parallel, a significant decrease of CD133 in renal progenitor cells and in their derived EVs was observed in vitro after cell treatment with a combination of glucose and albumin overload, mimicking the diabetic condition. These data indicate that the level of CD133+ uEVs may represent an easily accessible marker of renal normal physiology and could provide information on the "reservoir" of regenerating cells within tubules.

Early effects of first-line treatment with anti-interleukin-6 receptor antibody tocilizumab for chronic active antibody-mediated rejection in kidney transplantation.

INTRODUCTION: Chronic active antibody-mediated rejection (cAMR) is a major determinant of late allograft failure. Rituximab/immunoglobulins (IVIg) + plasma exchange (PLEX) showed controversial results in cAMR treatment. Tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, has been recently used as rescue therapy in patients non-responsive to rituximab/IVIg/PLEX with favorable outcomes. Whether TCZ acts "per se" or requires a priming effect from previous treatments is currently unknown. METHODS: Fifteen patients with cAMR were treated with TCZ as a first-line therapy and followed for a median time of 20.7 months. RESULTS: Despite the majority of patients experiencing advanced transplant glomerulopathy (TG) at diagnosis (60% with cg3), glomerular filtration rate and proteinuria stabilized during the follow-up, with a significant reduction in donor-specific antibodies. Protocol biopsies after 6 months demonstrated significant amelioration of microvascular inflammation and no TG, C4d deposition, or IF/TA progression. Gene-expression and immunofluorescence analysis showed upregulation of three genes (TJP-1, AKR1C3, and CASK) involved in podocyte, mesangial, and tubular restoration. CONCLUSION: Tocilizumab adopted as a first-line approach in cAMR was associated with early serological and histological improvements and functional stabilization even in advanced TG, suggesting a role for the use of TCZ alone with the avoidance of unnecessary previous immunosuppressants.

Cold intolerance and neuropathic pain after peripheral nerve injury in upper extremity.

Cold intolerance and pain can be a substantial problem in patients with peripheral nerve injury. We aimed at investigating the relationships among sensory recovery, cold intolerance, and neuropathic pain in patients affected by upper limb peripheral nerve injury (Sunderland type V) treated with microsurgical repair, followed by early sensory re-education. In a cross-sectional clinical study, 100 patients (male/female 81/19; age 40.5 ± 14.8 years and follow-up 17 ± 5 months, mean ± SD), with microsurgical nerve repair and reconstruction in the upper extremity and subsequent early sensory re-education, were evaluated, using Cold Intolerance Symptoms Severity questionnaire-Italian version (CISS-it, cut-off pathology >30/100 points), CISS questionnaire-12 item version (CISS-12, 0-46 points-grouping: healthy that means no cold intolerance [0-14], mild [15-24], moderate [25-34], severe [35-42], very severe [43-46] cold intolerance), probability of neuropathic pain (DouleurNeuropathique-4; [DN4] 4/10), deep and superficial sensibility, tactile threshold (monofilaments), and two-point discrimination (cutoff S2; Medical Research Council scale for sensory function; [MRC-scale]). A high CISS score is associated with possible neuropathic pain (DN4 ≥ 4). Both a low CISS-it score (ie, < 30) and DN4 < 4 is associated with good sensory recovery (MRC ≥ 2). In conclusion patients affected by upper limb peripheral nerve injuries with higher CISS scores more often suffer from cold intolerance and neuropathic pain, and the better their sensory recovery is, the less likely they are to suffer from cold intolerance and neuropathic pain.

Relationship between early proteinuria and long term outcome of kidney transplanted patients from different decades of donor age.

BACKGROUND: Proteinuria after kidney transplantation portends a worse graft survival. However the magnitude of proteinuria related to patient and graft survival and its correlation with donor and recipient characteristics are poorly explored. METHODS: This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages. Proteinuria cut off was set at 0.5 g/day. RESULTS: Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8). 1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (Hazard Ratio 2.77 vs Hazard Ratio 2.46). Low-grade proteinuria (0.2-0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors > 50 years old (Odd Ratio 2.3). CONCLUSIONS: Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia among others).

Recurrent IgA nephropathy after renal transplantation and steroid withdrawal.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis; the reported recurrence rate of IgAN after renal transplantation is as high as 13%-50%. The impact of immunosuppressive therapy and steroid withdrawal on the risk of recurrence of IgAN is still under debate. We performed a retrospective single-center study, selecting 123 kidney transplants (rtx) in 120 patients, between January 1995 and December 2012, with IgAN on the native kidney. In 51 of 123 transplants, at least one post-transplantation biopsy for clinical indication was performed; in 28 of 51 transplants, IgAN recurrence (IgANr) was demonstrated. This group (G1; N = 28) was compared with a group without IgANr (G2; N = 23). In our study, clinically evident IgANr rate was 54.9% (28/51) on biopsied patients. At discharge, the use of the immunosuppressant drugs (tacrolimus, cyclosporine A, mycophenolate mofetil, azathioprine, mTor inhibitors) was not associated with an increased risk of IgANr (P = NS). At discharge, all patients were steroid treated. Neither the use of tacrolimus, mycophenolate mofetil, nor mTor inhibitors (mTori) at biopsy time were associated with IgANr. However, IgANr was significantly higher in patients who experienced steroid withdrawal at any post-transplantation time (OR 7.7 P = .03). The median time to recurrence after steroid withdrawal was 59 months (min 4.18, max 113.2).

Detection of Angiotensin II type I-receptor antibodies in transplant glomerulopathy.

BACKGROUND: Transplant glomerulopathy (TG) is an important cause of late graft loss. The role of angiotensin type 1-receptor antibodies (AT1 R-Ab) in TG is not known. METHODS: All the TG cases (N = 137) between January 2007 and December 2014 (N = 1410) were analyzed. Donor-specific anti-HLA antibodies (DSA) at the time of biopsy and AT1 R-Ab IgG (positive, >17 UI/mL; "at risk," 10-17 UI/mL; negative, <10 UI/mL) in pre-transplant sera (PT-Ab) and at biopsy time (BT-Ab) were studied. RESULTS: AT1 R-PT-Ab+ and AT1 R-BT-Ab+ patients were 16.5% (51.5% "at risk") and 11.5% (27.4% "at risk"), respectively. Clinical correlations were found between AT1 R-Ab and HCV infection, number of transplants, and age. Considering Banff scores, ptc was higher in DSA+ patients vs AT1 R-PT-Ab+ (P = 0.002) or AT1 R-BT-Ab+ (P = 0.001) without differences in g and chronicity score (ci + ct); cg showed lower scores in DSA+ patients vs AT1 R-BT-Ab+ (P = 0.001). Graft survival was not influenced by the presence of AT1 R-Ab, AT1-R-Ab titer or MFI, but we observed a longer graft survival in patients with both AT1 R-BT-Ab+ or "at risk" and DSA+ vs patients positive only for DSA (P = 0.02), for AT1 R-BT-Ab (P = 0.019) or AT1 R-BT-Ab "at risk" (P = 0.039). CONCLUSION: AT1 R-Ab showed no independent prognostic role in TG in this pilot analysis.

De Novo Bladder Urothelial Neoplasm in Renal Transplant Recipients: A Retrospective, Multicentered Study.

BACKGROUND AND OBJECTIVES: Renal transplant recipients (RTRs) have a 2- to 7-fold risk of developing a neoplasm compared to general population. Bladder urothelial neoplasms in this cohort has an incidence of 0.4-2%. Many reports describe a more aggressive behavior. The objective of this study is to describe oncologic characteristics of bladder urothelial neoplasms in RTRs and to evaluate its recurrence, progression, and survival rates. METHODS: A retrospective multicentered study was performed evaluating all de novo bladder urothelial neoplasms cases in RTRs from 1988 to 2014. Descriptive statistical analysis and evaluation of recurrence, progression, and survival rates were performed. RESULTS: A total of 28 de novo bladder transitional cell carcinomas (TCCs) were identified (incidence rate 0.64%). Cancer-specific survival rates were 100, 75, and 70% after 1, 5, and 10 years, respectively. Age at diagnosis superior to 60 years was found to be a statistically significant variable for recurrence risk. Progression rate was 14%. Presence of CIS was significantly associated with progression. All cancer-specific deaths were in the high-risk group and all were progressions from non-muscle invasive to muscle invasive bladder cancer. CONCLUSIONS: Bladder urothelial neoplasms following renal transplant is associated with a trend toward worst prognosis. Early aggressive treatments, such as early radical cystectomy, might be advisable to reduce cancer-specific deaths.

Glycemic pattern in diabetic patients on hemodialysis: continuous glucose monitoring (CGM) analysis.

BACKGROUND/AIMS: Recent evidences suggest that hemodialysis (HD) induces glycemic variations in diabetic patients. Continuous glucose monitoring (CGM) devices measure interstitial glucose in a 'Holter-like' manner thereby improving the glycemic control assessment method. METHODS: A CGM device (Medtronic iPRO) was used on 12 diabetic patients with chronic HD for 6 days to assess intra- and extra-dialytic interstitial glucose. RESULTS: In all enrolled patients, HD was associated with a decrease of interstitial glucose values. Intradialytic glucose nadir was 79 mg/dl and it was reached at the third hour after the beginning of the session. At the end of HD, interstitial glucose increased in all patients and a glycemic peak (187 mg/dl) occurred after an average time of 2.5 h. No episodes of nocturnal hypoglycemia occurred. CONCLUSION: HD is associated with significant intradialytic reduction of glycemia and postdialytic hyperglycemia. CGM devices result in better monitoring of glycemic trends in diabetic patients on chronic HD and could improve insulin management.

Absence of IL-6 Receptor Blockade Effect on the Outcomes of Transplant Glomerulopathy in the Absence of Anti-HLA Donor-specific Antibodies.

Background: Transplant glomerulopathy (TG) is the hallmark of chronic antibody-mediated rejection but often occurs without anti-HLA donor-specific antibodies (DSAs) in the assumption that other DSAs may be the effectors of the tissue injury. Recently, we reported a positive effect of interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ) in TG/DSA+. In the present study, we investigate the effect of TCZ in a cohort of TG cases without detectable anti-HLA DSAs. Methods: Single-center retrospective analysis of TG cases without anti-HLA DSAs (TG/DSA) treated with TCZ for chronic antibody-mediated rejection as first-line therapy evaluated through clinical, protocol biopsies, and gene expression analyses was included. Results: Differently from TG/DSA+, TG/DSA- showed a progressive reduction in the estimated glomerular filtration rate at 12 mo and after that with no significant modification in microvascular inflammation or C4d+. No upregulation in tight junction protein-1, aldo-keto reductase family 1 member C3, and calcium/calmodulin-dependent serine protein kinase, documented in TG/DSA+, was noted in post-TCZ biopsies. The reduction of microvascular inflammation was associated with natural killer-cell reduction in TG/DSA+, whereas TG/DSA- tends to maintain or increase periglomerular/interstitial infiltration. Conclusions: In the absence of anti-HLA DSAs, TG behavior seems not to be modified by IL-6 receptor blockade. These results are at variance with observational studies and previous trials with IL-6 inhibitors in TG associated with anti-HLA DSAs. These data may fuel the hypothesis of different mechanisms underlying TGs (including the potentially different roles of natural killer cells) and suggest carefully selecting patients with TG for clinical trials or off-label treatment based on their antidonor serologic status.

Different profiles of acute graft pyelonephritis among kidney recipients from standard or elderly donors.

Background: Acute graft pyelonephritis (AGPN) is a relatively common complication in kidney transplants (KTs); however, the effects on allograft function, diagnostic criteria, and risk factors are not well established. Methods: Retrospective analysis of all consecutive adult KTs was performed between 01 January 2011 and 31 December 2018 (follow-up ended on 31 December 2019) to examine the association between the diagnosis of AGPN (confirmed with magnetic resonance imaging [MRI]) during the first post-transplantation year and graft outcomes. Results: Among the 939 consecutive KTs (≈50% with donors ≥60 years), we identified 130 MRI-confirmed AGPN episodes, with a documented association with recurrent and multidrug-resistant bacterial urinary tract infections (UTIs) (p < 0.005). Ureteral stenosis was the only risk factor associated with AGPN (OR 2.9 [95% CI, 1.6 to 5.2]). KTs with AGPN had a decreased allograft function at the first year (ΔeGFR 6 mL/min/1.73 m2 [-2-15] in non-AGPN vs. -0.2 [-6.5-8.5] in AGPN, p < 0.001), with similar and negative profiles in KTs from standard or elderly donors. However, only KTs with AGPN and a donor <60 years showed reduced death-censored graft survival (p = 0.015); most of this subgroup received anti-thymocyte globulin (ATG) induction (40.4% vs. 17.7%), and their MRI presented either a multifocal AGPN pattern (73.9% vs. 56.7%) or abscedation (28.3% vs. 11.7%). No difference was noted in death-censored graft survival between early (<3 months post-KT) or late (3-12 months) AGPN, solitary/recurrent forms, or types of multidrug-resistant pathogens. Linear regression confirmed the independent role of multifocal pattern, abscedation, ATG induction, and donor age on the eGFR at the first year. Conclusion: AGPN, influenced by multifocal presentation, ATG induction, donor age, and abscedation, affects kidney function and significantly impacts allograft survival in KTs with donors <60 years.

Lung ultrasonography performed by nephrologist: COVID-19 as an opportunity to reveal ultrasound's full potential and usefulness in the dialysis room.

Background: Interest in point-of-care ultrasound (POCUS) and lung ultrasound (LUS) is growing in the nephrology and dialysis field, and the number of nephrologists skilled in what is proving to be the "5th pillar of bedside physical examination" is increasing. Patients on hemodialysis (HD) are at high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) and developing coronavirus disease 2019 (COVID-19) serious complications. Despite this, to our knowledge there are no studies to date that show the role of LUS in this setting, while there are many in the emergency room, where LUS proved to be an important tool, providing risk stratification and guiding management strategies and resource allocation. Therefore, it is not clear whether the usefulness and cut-offs of LUS highlighted in studies in the general population are reliable in dialysis, or whether variations, precautions and adjustments to this specific situation are necessary. Methods: This was a 1-year monocentric prospective observational cohort study of 56 HD patients with COVID-19. Patients underwent a monitoring protocol that included at first evaluation bedside LUS, using a 12-scan scoring system, by the same nephrologist. All data were prospectively and systematically collected. Outcomes. hospitalization rate, combined outcome [non-invasive ventilation (NIV + death)], mortality. Descriptive variables are presented as medians (interquartile range), or percentage. Univariate and multivariate analysis, as well as Kaplan-Meier (K-M) survival curves, were carried out. P was fixed at .05. Results: Median age was 78 years, 90% had at least one comorbidity (46% diabetics), 55% were hospitalized and 23% deaths. Median duration of disease was 23 days (14-34). A LUS score ≥11 represented a 13-fold risk of hospitalization, a 16.5-fold risk of combined outcome (NIV + death) vs risk factors such as age [odds ratio (OR) 1.6], diabetes (OR 1.2), male sex (OR 1.3) and obesity (OR 1.25), and a 7.7-fold risk of mortality. In the logistic regression, LUS score ≥11 is associated with the combined outcome with a hazard ratio (HR) of 6.1 vs inflammations indices such as CRP ≥9 mg/dL (HR 5.5) and interleukin-6 (IL-6) ≥62 pg/mL (HR 5.4). In K-M curves, survival drops significantly with LUS score above 11. Conclusions: In our experience of COVID-19 HD patients, LUS appeared to be an effective and easy tool, predicting the need for NIV and mortality better than "classic" known COVID-19 risk factors such as age, diabetes, male sex and obesity, and even better than inflammations indices such as CRP and IL-6. These results are consistent with those of the studies in the emergency room setting, but with a lower LUS score cut-off (11 vs 16-18). This is probably due to the higher global frailty and peculiarity of HD population, and emphasizes how nephrologists should themselves use LUS and POCUS as a part of their everyday clinical practice, adapting it to the peculiarity of the HD ward.

Non-adherence assessment to immunosuppressant therapy with a self-report questionnaire and intra-patient variability in renal transplantation: risk factors and clinical correlations.

BACKGROUND: Non-adherence (NA) to immunosuppressive drugs is to date considered a crucial issue in kidney transplanted patients (KTRs), leading to de-novo donor-specific anti-HLA antibodies (dnDSA) development, acute and chronic rejection, and at least graft loss. However, NA assessment is challenging, often leading to underestimation in real-life settings. METHODS: NA evaluation in all KTRs referred to our post-transplantation clinic in the period between 01/01-15/07/2018 with self-report questionnaire combined to intra-patient variability (IPV) of the pivotal immunosuppressive drug (based on trough levels of tacrolimus/mTOR inhibitor). RESULTS: Based on both questionnaire and IPV, 86 out of the 504 tested KTRs (17%) were classified as NA. Male gender (OR, 2.0; 95% confidence interval [CI], 1.2 to 3.4), high educational level (OR for KTRs with a degree, 1.8 [95% CI, 1.0 to 3.1]), employment (OR, 2.0 [95% CI, 1.2 to 3.3]), young age at transplantation (P=0.017), longer time on the waiting list and after transplantation (P=0.027 and 0.049 respectively) were all associated with NA. High IPV was mostly documented in KTRs treated with the twice-daily formulation of the immunosuppressive drug (OR, 1.5 [95% CI, 1.0 to 2.1]) and better associated with dnDSA appearance (OR, 2.1 [95% CI, 1.1 to 3.9]). CONCLUSIONS: NA is a significant problem, difficult to assess, and can lead to dnDSA development also in our population. Identifying risk factors for NA might be an underestimated tool to improve graft and patient outcome in KTRs.

Relationship between Cytomegalovirus Viremia and Long-Term Outcomes in Kidney Transplant Recipients with Different Donor Ages.

OBJECTIVES: To explore the Cytomegalovirus (CMV) burden on the long-term post-transplant course in different donor ages, we evaluated the incidence and risk factors for CMV in our kidney-transplanted patients (KTs) with extensive adoption of expanded-criteria donors (ECDs). METHODS: Retrospective evaluation of 929 consecutive first KTs (49.5% receiving an organ from a donor ≥ 60 years) performed between 01-2003 and 12-2013. Overall survival was estimated using Kaplan-Meier curves; cumulative incidence function was additionally analyzed to consider the potential role of death with a functioning graft as a competitive event with graft dysfunction and to avoid overestimation. Apart from regular DNAemia monitoring in all patients, prophylaxis was adopted in high-risk groups (D+/R- or recipients of anti-thymocyte globulin induction), with pre-emptive therapy in the remaining groups. RESULTS: CMV incidence was 19.5% (4-34.9% according to serostatus combination: D-/R-, D-/R+, D+/R+, D+/R-). Donor and recipient age, recipient pre-transplant hypertension, DR antigen compatibility, cold ischemia time, and post-transplant early complications, including rejection, urologic and renal artery stenosis, and lower renal function and proteinuria ≥ 0.5 g/day at one year after KT were associated with CMV. CMV determined lower death-censored graft survival (DCGS) (p < 0.01), with a prominent effect in R+ (p < 0.01) and without impact in R- (p = 0.32 in D-/R- and p = 0.006 in D+/R-). Interestingly, CMV occurrence influenced DCGS only in KTs who received grafts from donors < 50 or 50-69 years old (p < 0.01), while it was not significant with older donors (p = 0.07). The analysis of the cumulative incidence of graft loss accounting for death as a competing risk confirmed all these findings. In multivariate analysis, CMV replication/disease in the first year was an independent predictor for DCGS (HR 1.73 [1.3-2.3]). CONCLUSIONS: In a large population with extensive ECD adoption, CMV viremia in the first year demonstrates its harmful effect with an independent role for graft loss and significant impact among R+ recipients and KTs with donors < 70 years.

Pigtail Suture Stents Significantly Reduce Stent-related Symptoms Compared to Conventional Double J Stents: A Prospective Randomized Trial.

BACKGROUND: Double J (DJ) ureteral stents are commonly inserted after ureteroscopy (URS) procedures for stone treatment. However, stent-related symptoms are still a major issue. OBJECTIVE: To determine whether a commercially available pigtail suture stent (PSS) can reduce stent-related symptoms compared to a conventional DJ stent after uncomplicated URS. DESIGN SETTING AND PARTICIPANTS: We designed a randomized, single-blind, parallel-group trial from January to November 2020. The inclusion criteria were stone-free URS without intraprocedural complications. Patients with distal ureteral stones were excluded. INTERVENTION: Insertion of a PSS or DJ stent after URS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the Urinary Symptom Index score on the Ureteral Stent Symptoms Questionnaire (USSQ) 2 wk after URS. Secondary endpoints were USSQ domain scores and responses to individual USSQ questions at 2 d and 2 wk after surgery. RESULTS AND LIMITATIONS: A total of 78 patients were randomized and treated according to protocol. The Urinary Symptom Index score (p = 0.004), overall Visual Analogue Scale (VAS) score (p = 0.022), and the percentage of patients complaining of pain (63.9% vs 86.1%, p = 0.029) were significantly in favor of PSS at both 2 d and 2 wk after URS. At 2 d, the VAS score among patients with pain (p = 0.025) and the General Health Index score (p = 0.036) were significantly better in the PSS group. No severe complications occurred in either group. Study limitations are the exclusion of patients with distal ureteral stones and the limited sample size. CONCLUSIONS: PSS significantly reduced stent-related symptoms after URS, in particular urinary symptoms and pain, compared to conventional DJ stents, and showed a good safety profile. PATIENT SUMMARY: Stents are hollow tubes placed in the passage between the kidney and the bladder (ureter). The standard stent has two coiled ends (double J stent) to keep it in place in both the kidney and the bladder. We tested a commercial stent with two strings at the bladder end (pigtail suture stent) after procedures to remove stones from the upper urinary tract and found that it caused less stent-related symptoms compared to a double J stent.This trial is registered at Clinicaltrials.gov as NCT03344120.

Hemodialysis arteriovenous fistula ligation after renal transplantation: Impact on graft resistive index.

BACKGROUND: Kidney allograft resistive index (RI) is prognostic for graft and recipient survivals. Recipient hemodynamics could influence RI. In particular, dialysis arteriovenous fistula (AVF) has been involved in heart function changes, reversible after AVF ligation. Knowledge about AVF and RI is lacking. In this study, we prospectively evaluated RI changes after AVF ligation in kidney transplanted patients. METHODS: We enrolled 22 stable transplanted patients. Mean RI was measured before AVF ligation (T0), 18 to 24 h (T1) and 6 months (T6) after surgery; mean blood pressure (mBP), heart rate (HR), serum creatinine (sCr), estimated glomerular filtration rate (eGFR), 24 h proteinuria (24 h-P), immunosuppressive drug blood levels (IS) and antihypertensive drugs were also recorded. RESULTS: AVF ligation was performed 3.1 years (IQR: 2.1-3.8) after transplantation. Median AVF flow (Qa) was 1868 mL/min (IQR: 1538-2712) and 8 AVF were classified as high flow (Qa ≥ 2 L/min). At baseline, median sCr was 1.32 mg/dL (IQR: 1.04-1.76) and median eGFR was 57.1 mL/min. Median RI was 0.71 at T0, 0.69 at T1, 0.66 at T6. RI reduction at T1 and T6 was statistically significant (p < 0.05 and p < 0.001 respectively); in particular, 90.4% of patients had persistently improved values at T6. Furthermore, mBP increased while HR decreased. These changes were independent from sCr, 24 h-P, IS, antihypertensive drugs number, Qa and AVF type. CONCLUSIONS: AVF ligation improves kidney allograft RI; it may reflect better kidney perfusion.

Monoclonal gammopathy of undetermined significance coexisting in patients undergoing kidney transplantation does not adversely influence post-graft clinical outcome.

BACKGROUND: Management of patients with oncohaematological disorders such as monoclonal gammopathy of undetermined significance (MGUS) is a frequent problem in pre-transplant work-up. Insights on disease progression and long-term functional outcomes are still lacking in this setting. METHODS: This was a retrospective analysis on all patients with MGUS who underwent kidney transplant (KT) at our centre between 1 January 2000 and 31 December 2017 (cases, n = 65). Patients were matched with a control group (KTs with similar characteristics but without history of haematological disease, controls, n = 1079). Primary endpoints were graft and patient survival; secondary endpoints were causes of graft failure, patient death, occurrence of allograft rejection, post-transplant neoplasia (not correlated to previous disorder) and/or infectious episodes. RESULTS: The MGUS and control groups had a similar mean age [60 (29-79) versus 55.2 (19.3-79.5) years, respectively] and percentage of males (69.2% versus 64.6%, respectively). Median follow-up time since KT was 3.5 years (0-14) in cases and 8.3 years (0-14.9) in controls. All MGUS patients underwent KT following extensive multidiscliplinary investigations. No differences were found between cases and controls regarding patient and graft survival or post-transplant complications except for lower incidence of infections (58.7% versus 69.8%, P = 0.019) and increased use of mTOR inhbitors (30.3% versus 14.7%, P = 0.001) in MGUS. MGUS isotype did not influence graft and patient survival. The absence of difference in patients and graft survival was also confirmed in an adjunctive analysis where MGUS were compared with controls (ratio 1:2) matched for recipient age, gender, number of transplantations and transplant period. CONCLUSION: Patients with MGUS may undergo KT without significantly increased risks of complications, provided that appropriate diagnostic procedures are carefully followed. Multidiscipline-based studies are crucial for establishing well designed pre- and post-transplant protocols for the best management of patients with coexisting MGUS and end-stage renal disease.