Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players.

BACKGROUND: Inherited kidney diseases are one of the leading causes of chronic kidney disease (CKD) that manifests before the age of 30 years. Precise clinical diagnosis of early-onset CKD is complicated due to the high phenotypic overlap, but genetic testing is a powerful diagnostic tool. We aimed to develop a genetic testing strategy to maximize the diagnostic yield for patients presenting with early-onset CKD and to determine the prevalence of the main causative genes. METHODS: We performed genetic testing of 460 patients with early-onset CKD of suspected monogenic cause using next-generation sequencing of a custom-designed kidney disease gene panel in addition to targeted screening for c.428dupC MUC1. RESULTS: We achieved a global diagnostic yield of 65% (300/460), which varied depending on the clinical diagnostic group: 77% in cystic kidney diseases, 76% in tubulopathies, 67% in autosomal dominant tubulointerstitial kidney disease, 61% in glomerulopathies and 38% in congenital anomalies of the kidney and urinary tract. Among the 300 genetically diagnosed patients, the clinical diagnosis was confirmed in 77%, a specific diagnosis within a clinical diagnostic group was identified in 15%, and 7% of cases were reclassified. Of the 64 causative genes identified in our cohort, 7 (COL4A3, COL4A4, COL4A5, HNF1B, PKD1, PKD2 and PKHD1) accounted for 66% (198/300) of the genetically diagnosed patients. CONCLUSIONS: Two-thirds of patients with early-onset CKD in this cohort had a genetic cause. Just seven genes were responsible for the majority of diagnoses. Establishing a genetic diagnosis is crucial to define the precise aetiology of CKD, which allows accurate genetic counselling and improved patient management.

Clinical and genetic characterization of a cohort of proteinuric patients with biallelic CUBN variants.

BACKGROUND: Proteinuria is a well-known risk factor for progressive kidney impairment. Recently, C-terminal cubilin (CUBN) variants have been associated with isolated proteinuria without progression of kidney disease. METHODS: Genetic testing of 347 families with proteinuria of suspected monogenic cause was performed by next-generation sequencing of a custom-designed kidney disease gene panel. Families with CUBN biallelic proteinuria-causing variants were studied at the clinical, genetic, laboratory and pathologic levels. RESULTS: Twelve families (15 patients) bearing homozygous or compound heterozygous proteinuria-causing variants in the C-terminal CUBN gene were identified, representing 3.5% of the total cohort. We identified 14 different sequence variants, five of which were novel. The median age at diagnosis of proteinuria was 4 years (range 9 months to 44 years), and in most cases proteinuria was detected incidentally. Thirteen patients had moderate to severe proteinuria at diagnosis without nephrotic syndrome. These patients showed lack of response to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, normal kidney biopsy and preservation of normal kidney function over time. The two remaining patients presented a more severe phenotype, likely caused by associated comorbidities. CONCLUSIONS: Identification of C-terminal pathogenic CUBN variants is diagnostic of an entity characterized by glomerular proteinuria, normal kidney histology and lack of response to ACEi/ARB treatment. This study adds evidence and increases awareness about albuminuria caused by C-terminal variants in the CUBN gene, which is a benign condition usually diagnosed in childhood with preserved renal function until adulthood.

Prospective comparative study of postoperative systemic inflammatory syndrome in robot-assisted vs. open kidney transplantation.

PURPOSE: Robot-assisted kidney transplant (RAKT) recently proved to provide functional results similar to the preferred open kidney transplant (OKT), but with inferior wound morbidity. In a comparative prospective study, we explored the systemic inflammatory response syndrome (SIRS) after KT and compared OKT with RAKT. METHODS: Forty-nine patients underwent pre-emptive ABO-compatible kidney transplantations (KT) between January 2017 and December 2018 in 2 centers: 25 RAKT, 24 OKT. Postoperative SIRS was biologically assessed by serum markers (NGAL, CRP and IL-6) measured at: T0 (preoperative/baseline), T1(H1), T2(H6), T3(H12), T4(H24), T5(D2), T6(D3) and T7(D5) after KT. RESULTS: Inflammatory markers + eGFR were assessed in OKT vs. RAKT. IL-6 peak value occurred at H6 and reached ×9 from baseline. CRP peak occurred at H24 and reached ×28 from baseline (All P < 0.05). NGAL decreased after surgery with a plateau (divided by 2 from baseline) from H12 to D5. There was no significant difference in IL-6, CRP and NGAL kinetics and peak values between RAKT and OKT (All P > 0.05). Serum creatinine and eGFR on postoperative days 1, 3 and 7 were similar in RAKT and OKT (All P > 0.05). Delayed graft function was not observed. CONCLUSION: In this exploratory study, the biological evaluation of postoperative SIRS after living-donor kidney transplant revealed no significant difference between OKT and RAKT and similar functional outcomes in the short term. These results highlight the safety of RAKT as an alternative to OKT in this setting.

Advantages of plasmatic CXCL-10 as a prognostic and diagnostic biomarker for the risk of rejection and subclinical rejection in kidney transplantation.

This study evaluate the potential of plasmatic CXCL-10 (pCXCL-10) as a pre&post transplantation prognostic and diagnostic biomarker of T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR) and subclinical rejection (SCR) risk in adult kidney recipients considering BKV and CMV infections as possible clinical confounder factors. Twenty-eight of 100 patients included experienced rejection (TCMR:14; ABMR:14); 8 SCR; 13 and 16 were diagnosed with BKV and CMV infection, respectively. Pre-transplantation pCXCL-10 was significantly increased in TCMR and ABMR and post-transplantation in TCMR, ABMR and SCR compared with nonrejectors. All CMV+ patients showed pCXCL-10 levels above the cutoff values established for rejection whereas the 80% of BKV+ patients showed pCXCL-10 concentration < 100 pg/mL. pCXCL-10 could improve pre-transplantation patient stratification and immunosuppressive treatment selection according to rejection risk; and after kidney transplantation could be a potential early prognostic biomarker for rejection. Clinical confounding factor in BKV+ and particularly in CMV+ patients must be discarded.

Clinical and Genetic Features of Autosomal Dominant Alport Syndrome: A Cohort Study.

RATIONALE & OBJECTIVE: Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected. OBSERVATIONS: A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families), whereas 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 (95% CI, 58-73) years, without significant differences across sex (P=0.8), causative genes (P=0.6), or type of variant (P=0.9). Microhematuria was the most common kidney manifestation (92.1%), and extrarenal features were rare. Findings on kidney biopsies ranged from normal to focal segmental glomerulosclerosis. The slope of estimated glomerular filtration rate change was-1.46 (-1.66 to-1.26) mL/min/1.73m2 per year for the overall group, with no significant differences between ADAS genes (P=0.2). LIMITATIONS: The relatively small size of this series from a single country, potentially limiting generalizability. CONCLUSIONS: Patients with ADAS have a wide spectrum of clinical presentations, ranging from asymptomatic to kidney failure, a pattern not clearly related to the causative gene or type of variant. The diversity of ADAS phenotypes contributes to its underdiagnosis in clinical practice.

Deciphering transplant outcomes of expanded kidney allografts donated after controlled circulatory death in the current transplant era. A call for caution.

Outcomes of kidney transplantation (KT) after controlled circulatory death (cDCD) with highly expanded criteria donors (ECD) and recipients have not been thoroughly evaluated. We analyzed in a multicenter cohort of 1161 consecutive KT, granular baseline donor and recipient factors predicting transplant outcomes, selected by bootstrapping and Cox proportional hazards, and were validated in a contemporaneous European KT cohort (n = 1585). 74.3% were DBD and 25.7% cDCD-KT. ECD-KT showed the poorest graft survival rates, irrespective of cDCD or DBD (log-rank < 0.001). Besides standard ECD classification, dialysis vintage, older age, and previous cardiovascular recipient events together with low class-II-HLA match, long cold ischemia time and combining a diabetic donor with a cDCD predicted graft loss (C-Index 0.715, 95% CI 0.675-0.755). External validation showed good prediction accuracy (C-Index 0.697, 95%CI 0.643-0.741). Recipient older age, male gender, dialysis vintage, previous cardiovascular events, and receiving a cDCD independently predicted patient death. Benefit/risk assessment of undergoing KT was compared with concurrent waitlisted candidates, and despite the fact that undergoing KT outperformed remaining waitlisted, remarkably high mortality rates were predicted if KT was undertaken under the worst risk-prediction model. Strategies to increase the donor pool, including cDCD transplants with highly expanded donor and recipient candidates, should be performed with caution.

Cellular Immunity to Predict the Risk of Cytomegalovirus Infection in Kidney Transplantation: A Prospective, Interventional, Multicenter Clinical Trial.

BACKGROUND: Improving cytomegalovirus (CMV) immune-risk stratification in kidney transplantation is highly needed to establish guided preventive strategies. METHODS: This prospective, interventional, multicenter clinical trial assessed the value of monitoring pretransplant CMV-specific cell-mediated immunity (CMI) using an interferon-γ release assay to predict CMV infection in kidney transplantation. One hundred sixty donor/recipient CMV-seropositive (D+/R+) patients, stratified by their baseline CMV (immediate-early protein 1)-specific CMI risk, were randomized to receive either preemptive or 3-month antiviral prophylaxis. Also, 15-day posttransplant CMI risk stratification and CMI specific to the 65 kDa phosphoprotein (pp65) CMV antigen were investigated. Immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids in 80% of patients, whereas 20% received thymoglobulin induction therapy. RESULTS: Patients at high risk for CMV based on pretransplant CMI developed significantly higher CMV infection rates than those deemed to be at low risk with both preemptive (73.3% vs 44.4%; odds ratio [OR], 3.44 [95% confidence interval {CI}, 1.30-9.08]) and prophylaxis (33.3% vs 4.1%; OR, 11.75 [95% CI, 2.31-59.71]) approaches. The predictive capacity for CMV-specific CMI was only found in basiliximab-treated patients for both preemptive and prophylaxis therapy. Fifteen-day CMI risk stratification better predicted CMV infection (81.3% vs 9.1%; OR, 43.33 [95% CI, 7.89-237.96]). CONCLUSIONS: Pretransplant CMV-specific CMI identifies D+/R+ kidney recipients at high risk of developing CMV infection if not receiving T-cell-depleting antibodies. Monitoring CMV-specific CMI soon after transplantation further defines the CMV infection prediction risk. Monitoring CMV-specific CMI may guide decision making regarding the type of CMV preventive strategy in kidney transplantation. CLINICAL TRIALS REGISTRATION: NCT02550639.

Valvular heart disease and calcification in CKD: more common than appreciated.

Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10-20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications.

From Inflammation to the Onset of Fibrosis through A2A Receptors in Kidneys from Deceased Donors.

Pretransplant graft inflammation could be involved in the worse prognosis of deceased donor (DD) kidney transplants. A2A adenosine receptor (A2AR) can stimulate anti-inflammatory M2 macrophages, leading to fibrosis if injury and inflammation persist. Pre-implantation biopsies of kidney donors (47 DD and 21 living donors (LD)) were used to analyze expression levels and activated intracellular pathways related to inflammatory and pro-fibrotic processes. A2AR expression and PKA pathway were enhanced in DD kidneys. A2AR gene expression correlated with TGF-ß1 and other profibrotic markers, as well as CD163, C/EBPß, and Col1A1, which are highly expressed in DD kidneys. TNF-α mRNA levels correlated with profibrotic and anti-inflammatory factors such as TGF-ß1 and A2AR. Experiments with THP-1 cells point to the involvement of the TNF-α/NF-κB pathway in the up-regulation of A2AR, which induces the M2 phenotype increasing CD163 and TGF-ß1 expression. In DD kidneys, the TNF-α/NF-κB pathway could be involved in the increase of A2AR expression, which would activate the PKA-CREB axis, inducing the macrophage M2 phenotype, TGF-ß1 production, and ultimately, fibrosis. Thus, in inflamed DD kidneys, an increase in A2AR expression is associated with the onset of fibrosis, which may contribute to graft dysfunction and prognostic differences between DD and LD transplants.

Apolipoprotein A-Ib as a biomarker of focal segmental glomerulosclerosis recurrence after kidney transplantation: diagnostic performance and assessment of its prognostic value - a multi-centre cohort study.

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) is a serious complication after kidney transplantation. FSGS relapse is suspected by a sudden increase in proteinuria but there is not an accurate noninvasive diagnostic tool to confirm this entity or to detect patients at risk. We aimed to validate the diagnostic performance of ApoA-Ib to detect FSGS relapses by measuring urinary ApoA-Ib in a retrospective cohort of 61 kidney transplanted patients (37 FSGS and 24 non-FSGS). In addition, to assess the ApoA-Ib predictive ability, ApoA-Ib was measured periodically in a prospective cohort of 13 idiopathic FSGS patients who were followed during 1 year after transplantation. ApoA-Ib had a sensitivity of 93.3% and a specificity of 90.9% to diagnose FSGS relapses, with a high negative predictive value (95.2%), confirming our previous results. In the prospective cohort, ApoA-Ib predated the recurrence in four of five episodes observed. In the nonrelapsing group (n = 9), ApoA-Ib was negative in 37 of 38 samples. ApoA-Ib has the potential to be a good diagnostic biomarker of FSGS relapses, providing a confident criterion to exclude false positives even in the presence of high proteinuria. It has also the potential to detect patients at risk of relapse, even before transplantation.

Robotic kidney transplantation: one year after the beginning.

INTRODUCTION: Kidney transplantation (KT) is the preferred treatment for patients with end-stage renal disease (ESRD). To reduce the morbidity of the open surgery, a robotic-assisted approach has been recently introduced. Our aim is to evaluate surgical and functional results on 17 cases of robotic-assisted kidney transplantation (RAKT) performed at the same institution. MATERIALS AND METHODS: From July 2015 to June 2016, we performed 17 cases of RAKT from living donors in pre-emptive patients, who underwent laparoscopic nephrectomy. A prospective pilot study was made at Fundació Puigvert (Barcelona), evaluating functional and surgical outcomes. In this series, we considered the functional results, surgical outcomes and complications rates. RESULTS: Seventeen patients successfully underwent RAKT, in particular surgical console time was 181 min (150-200) with vascular suture time 42 min (32-48), and estimated blood loss <70 ml. Overall ischemia time was 98.9 min (84-140). No patient was converted to open transplantation. No major surgical intra-operative complications were observed. The mean post-operative serum creatinine level 160 µmol/L (81-479). We reported a case of delayed graft function (DGF), one case of graft arterial thrombosis and one case of intraperitoneal hematoma. No anastomosis revision and wounds infections occurred. CONCLUSION: RAKT with regional hypothermia appears to be a safe surgical procedure in a properly selected group of patients. The potential advantages of RAKT are related to the quality of the vascular anastomosis, the possible lower complication rate and the shorter recovery of the recipients.

Urinary miR-155-5p and CXCL10 as prognostic and predictive biomarkers of rejection, graft outcome and treatment response in kidney transplantation.

AIMS: MicroRNAs (miRNAs) may be useful biomarkers of rejection and allograft outcome in kidney transplantation. Elevated urinary CXCL10 levels have been associated with acute rejection (AR) and may predict allograft failure. We examined the correlation of miRNA, CXCL10 levels and immunosuppressive drug exposure with AR and graft function in kidney transplant recipients. METHODS: Eighty de novo kidney transplant recipients were recruited from four European centres. All patients received tacrolimus, mycophenolate mofetil, and methylprednisolone. Urinary pellet expression of miR-142-3p, miR-210-3p and miR-155-5p was assessed by quantitative real-time polymerase chain reaction and urinary CXCL10 levels by enzyme-linked immunosorbent assay at the 1st week and the 1st , 2nd , 3rd and 6th months post-transplantation. RESULTS: Eight patients experienced AR. Before and during AR, patients showed a significant increase of urinary miR-142-3p, miR-155-5p and CXCL10 levels and a decrease of miR-210-3p levels. Receiver operating characteristic curve analysis showed that miR-155-5p (area under the curve = 0.875; P = 0.046) and CXCL10 (area under the curve = 0.865; P = 0.029) had excellent capacity to discriminate between rejectors and nonrejectors. The optimal cut-off values for the prognosis of AR were 0.51, with 85% sensitivity and 86% specificity for miR-155-5p and 84.73 pg ml-1 , with 84% sensitivity and 80% specificity for CXCL10. miR-155-5p and CXCL10 levels correlated with glomerular filtration rate. Levels of both biomarkers normalized after recovery of graft function. CONCLUSIONS: The regular early post-transplantation monitoring of urinary miR-155-5p and CXCL10 can help in the prognosis of AR and graft dysfunction. Large prospective randomized multicentre trials are warranted to refine our cut-off values and validate the clinical usefulness of these biomarkers.

Role of mTOR inhibitors for the control of viral infection in solid organ transplant recipients.

Appropriate post-transplant immunosuppressive regimens that avoid acute rejection, while reducing risk of viral reactivation, have been sought, but remain a chimera. Recent evidence suggesting potential regulatory and antiviral effects of mammalian target of rapamycin inhibitors (mTORi) is of great interest. Although the concept of an immunosuppressive drug with antiviral properties is not new, little effort has been made to put the evidence together to assess the management of immunosuppressive therapy in the presence of a viral infection. This review was developed to gather the evidence on antiviral activity of the mTORi against the viruses that most commonly reactivate in adult solid organ recipients: cytomegalovirus (CMV), polyomavirus, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and hepatitis C virus (HCV). A rapid review methodology and evaluation of quality and consistency of evidence based on the GRADE system was used. The existing literature was variable in nature, although indicating a potential advantage of mTORi in CMV, polyomavirus, and HHV8 infection, and a most doubtful relation with EBV and HCV infection. Several recommendations about the management of these infections are presented that can change certain current patterns of immunosuppression and help to improve the prognosis of the direct and indirect effects of viral infection in solid organ recipients.

Robotic kidney transplantation.

Kidney transplantation is the best treatment option for patients with end-stage renal disease owing to improved survival and quality of life compared with dialysis. The surgical approach to kidney transplantation has been somewhat stagnant in the past 50 years, with the open approach being the only available option. In this scenario, evidence of reduced surgery-related morbidity after the introduction of robotics into several surgical fields has induced surgeons to consider robot-assisted kidney transplantation (RAKT) as an alternative approach to these fragile and immunocompromised patients. Since 2014, when the RAKT technique was standardized thanks to the pioneering collaboration between the Vattikuti Urology Institute and the Medanta hospital (Vattikuti Urology Institute-Medanta), several centres worldwide implemented RAKT programmes, providing interesting results regarding the safety and feasibility of this procedure. However, RAKT is still considered an alternative procedure to be offered mainly in the living donor setting, owing to various possible drawbacks such as prolonged rewarming time, demanding learning curve, and difficulties in carrying out this procedure in challenging scenarios (such as patients with obesity, severe atherosclerosis of the iliac vessels, deceased donor setting, or paediatric recipients). Nevertheless, the refinement of robotic platforms through the implementation of novel technologies as well as the encouraging results from multicentre collaborations under the umbrella of the European Association of Urology Robotic Urology Section are currently expanding the boundaries of RAKT, making this surgical procedure a real alternative to the open approach.

High incidence of delayed graft function in HIV-infected kidney transplant recipients.

Kidney transplantation (KT) outcomes in human immunodeficiency virus (HIV)-infected recipients are under continuous research. High incidence of early post-transplant complications such as acute rejection has been observed. A multicenter study including HIV-infected patients who underwent KT in Spain, from 2001 to 2011, was performed. The study population included 108 recipients, 36 HIV-infected, and 72 matched HIV-negative KT recipients. HIV-infected recipients developed more delayed graft function (DGF) (52% vs. 21%, P < 0.001). One- and 3-year graft survival was 91.6% and 86.2% in HIV-infected patients, and 97.1% and 94.7% in HIV-negative patients (P = 0.052). In two-variate Cox analysis, HIV infection was not a predictor of graft loss after adjusting for time on dialysis, acute rejection, and DGF. Multivariate analysis for DGF revealed HIV-positive status as independent risk factor. We analyzed the evolution of immunosuppressive and antiretroviral therapy (ART). In HIV-infected patients tacrolimus trough levels were very high in the first week and significantly lower in the second week post-transplant (P = 0.042). Post-transplant ART was significantly changed: protease inhibitors use decreased (P = 0.034) and integrase inhibitor use increased (P < 0.001). DGF is another frequent early complication in HIV-infected recipients that can affect graft survival. Strategies to prevent DGF and antiretroviral regimes with less drug interactions could improve outcomes.

Correlation of X chromosome inactivation with clinical presentation of Fabry disease in a case report.

Fabry disease or also called Anderson-Fabry disease (FD) is a rare disease caused by pathogenic variants in the GLA gene, located on the X chromosome. This gene is involved in the metabolism of glycosphingolipids and its pathogenic variants cause a deficit or absence of α-galactosidase A causing the deposition of globotriaosylceramide throughout the body. Females have a variable phenotypic expression and a better prognosis than males. This is due to the X chromosome inactivation phenomenon. We present a clinical case of Fabry disease in a female with predominantly renal involvement and demonstrate how the X chromosome inactivation phenomenon is tissue dependent, showing preferential inactivation of the mutated allele at the renal level.

Comparative analysis of tools to predict rapid progression in autosomal dominant polycystic kidney disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease and shows a wide phenotype. Only patients with rapid progression (RP) are included in clinical trials or are approved to receive disease-modifying drugs. This study aims at comparing different available predictive tools in ADPKD with the Mayo classification (MC) identification of rapid progressors based on high total kidney volume (TKV) according to age. Methods: A total of 164 ADPKD patients were recruited retrospectively from a single centre. The performance of diverse tools to identify RP defined as being in MC categories 1C-1E was assessed. Results: A total of 118 patients were MC 1C-1E. The algorithm developed by the European Renal Association-European Dialysis and Transplant Association Working Group on Inherited Kidney Disorders/European Renal Best Practice had a low sensitivity in identifying MC 1C-1E. The sensitivity and specificity of TKV to predict RP depend on the cut-off used. A kidney length of >16.5 cm before age 45 years has high specificity but low sensitivity. Assessing the MC by ultrasonography had high levels of agreement with magnetic resonance imaging (MRI) data, especially for 1A, 1D and 1E. The estimated glomerular filtration rate (eGFR) decline was very sensitive but had low specificity. In contrast, the Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score was very specific but had poor sensitivity. Having hypertension before 35 years of age is a good clinical predictor of MC 1C-1E. Family history can be of help in suggesting RP, but by itself it lacks sufficient sensitivity and specificity. Conclusions: The MC by ultrasonography could be an option in hospitals with limited access to MRI as it performs well generally, and especially at the extremes of the MC, i.e. classes 1A, 1D and 1E. The eGFR decline is sensitive but not very specific when compared with the MC, whereas the PROPKD score is very specific but has low sensitivity. Integrating the different tools currently available to determine RP should facilitate the identification of rapid progressors among patients with ADPKD.

Three-dimensional Augmented Reality-guided Robotic-assisted Kidney Transplantation: Breaking the Limit of Atheromatic Plaques.

BACKGROUND: Robotic-assisted kidney transplantation (RAKT) has shown solid results as a minimally invasive alternative to the standard open approach (open kidney transplantation [OKT]). However, RAKT is still limited in those cases where the recipient's iliac vessels present atherosclerotic plaques, frequently found in elder patients and in those subjected to long-term hemodialysis. Unlike OKT, where the surgeon can palpate the arterial plaques, in minimally invasive surgery the haptic feedback is missing, making the vascular clamping and arteriotomy unsafe. OBJECTIVE: To employ three-dimensional (3D) imaging reconstruction using augmented reality (AR) to intraoperatively locate the plaques during the crucial steps of kidney transplantation. DESIGN, SETTING, AND PARTICIPANTS: Our study was conducted according to the Idea, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) model for surgical innovation. Three-dimensional virtual models were obtained from high-accuracy computed tomography scan imaging and superimposed on the vessels during RAKT using the Da Vinci console software. SURGICAL PROCEDURE: Three-dimensional AR-guided robotic-assisted kidney transplantation. MEASUREMENTS: The correspondence of virtual models with the real anatomy of patients was assessed comparing vessels' and plaques' measures. RESULTS AND LIMITATIONS: We tested the possibility of using the AR in the setting of vascular surgery by checking the correspondence of the virtual models to the real vessels. During the accuracy assessment, we investigated the anatomy of the iliac plaques and the capacity of the virtual models to correctly represent them. Finally, we tested the efficacy of the virtual model superimposition on the real vessels with plaques during RAKT in the recipients of living donor grafts. The main limitation consists in training needed to correctly superimpose virtual models on the real field. CONCLUSIONS: The employment of 3D AR allowed surgeons to overcome one of the main limitations of RAKT, setting the foundation to expand its indications to patients with advanced atheromatic vascular disease. PATIENT SUMMARY: The use of three-dimensional augmented reality guidance during kidney transplantation (KT) has the potential to "navigate" the surgeon during KT, allowing a safer procedure in patients with atheromatic vascular disease.

Recommendations for living donor kidney transplantation.

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.

Acute Renal Failure Secondary to an Unusual Familial Metabolic Myopathy.

Rhabdomyolysis is a major cause of acute kidney failure. The etiology is diverse, from full-blown crush syndrome to less frequent causes, such as metabolic myopathy. We describe the case of a 35-year-old male with a history of intermittent myalgias who was admitted to hospital with acute renal failure secondary to rhabdomyolysis. Moderate to intense diffuse uptake of technetium-99m was seen in soft tissues at scintigraphy. The diagnosis of metabolic myopathy was confirmed after careful workup and genetic testing.