Race-free estimated glomerular filtration rate equation in kidney transplant recipients:development and validation study

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients.DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials).PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021.MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P 30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m 2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m 2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P 30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P 30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys.TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.</p

Diverse molecular causes of unsolved autosomal dominant tubulointerstitial kidney diseases

Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is caused by mutations in one of at least five genes and leads to kidney failure usually in mid adulthood. Throughout the literature, variable numbers of families have been reported, where no mutation can be found and therefore termed ADTKD-not otherwise specified. Here, we aim to clarify the genetic cause of their diseases in our ADTKD registry. Sequencing for all known ADTKD genes was performed, followed by SNaPshot minisequencing for the dupC (an additional cytosine within a stretch of seven cytosines) mutation of MUC1. A virtual panel containing 560 genes reported in the context of kidney disease (nephrome) and exome sequencing were then analyzed sequentially. Variants were validated and tested for segregation. In 29 of the 45 registry families, mutations in known ADTKD genes were found, mostly in MUC1. Sixteen families could then be termed ADTKD-not otherwise specified, of which nine showed diagnostic variants in the nephrome (four in COL4A5, two in INF2 and one each in COL4A4, PAX2, SALL1 and PKD2). In the other seven families, exome sequencing analysis yielded potential disease associated variants in novel candidate genes for ADTKD; evaluated by database analyses and genome-wide association studies. For the great majority of our ADTKD registry we were able to reach a molecular genetic diagnosis. However, a small number of families are indeed affected by diseases classically described as a glomerular entity. Thus, incomplete clinical phenotyping and atypical clinical presentation may have led to the classification of ADTKD. The identified novel candidate genes by exome sequencing will require further functional validation

Persistent hypoglossal artery

It is well known that the internal carotid artery has no branches in the neck during postfetal life (von Lanz & Wachsmuth, 1955), but during embryonic development there are anastomotic connections between the internal carotid and basilar artery that rarely persist after intrauterine life (Hassen-Khodja et al. 1992; Widmann & Sumpio, 1992; De Caro et al. 1995). The most common anomaly found incidentally on angiography is a persisting trigeminal artery, but persistent hypoglossal, otic and proatlantal arteries can also be found (Reynolds et al. 1980; Ouriel et al. 1988; Salas et al. 1998). We report a rare example of a persistent hypoglossal artery in a 64 y old female cadaver, cause of death unknown, embalmed by standard mortuary procedures for dissection during the routine anatomy course. The persistent hypoglossal artery originated from the anteromedial wall of the left internal carotid artery 2.5 cm above the bifurcation (Fig.). It extended towards the hypoglossal canal. The diameter of its lumen was 1.5 mm. During its course in the neck, it was positioned anterior to the internal carotid artery and medial to the facial and lingual arteries, the posterior belly of the digastric muscle and the convexity of the hypoglossal nerve in the neck. At 1 cm above the convexity of the hypoglossal nerve in the neck, the artery gave rise to a branch that entered the skull through the carotid canal anteromedial to the internal carotid artery (Fig. 1) and joined the basilar artery. The medial branch of the hypoglossal artery crossed the internal carotid artery on its medial side and entered the skull together with the hypoglossal nerve and joined the basilar artery. We found no other anomalies in the cerebral arterial system

JC Virus in Kidney Transplant Population: Are We Cautious Enough?

The John Cunningham virus (JCV) is a polyomavirus that usually infects people at a young age and does not cause any symptoms in immunocompetent individuals. However, in immunocompromised individuals, such as kidney transplant recipients, JCV can cause severe and potentially fatal disease. Unfortunately, JCV has not been researched as extensively as the BK virus and is not mentioned in relevant kidney transplant guidelines. This lack of attention to JCV can lead to less consideration in kidney transplant patients’ care. Surveillance using locally available diagnostic methods is of the utmost importance. The presence of JCV can be diagnosed with urine decoy cells, viruria, or viremia verified by the PCR method. A low threshold for considering JCV as a possible cause of any neurological or renal dysfunction in kidney transplant recipients must be maintained. In such cases, kidney and brain biopsy are indicated. Maintaining the appropriate immunosuppression while avoiding over-immunosuppression to prevent JCV disease is crucial, and the approach should be individual, according to overall immunological risk. We hypothesize that the presence of the JCV can indicate overt immunosuppression and identify kidney transplant recipients more prone to opportunistic infections and diseases, including some malignancies. To explore that, future observational studies are needed

Histopathological features of time-zero kidney biopsy are predictive factors for posttransplant anemia

Posttransplant anemia is a common complication of kidney transplantation, associated with reduced graft survival and higher mortality. We aimed to determine the association of posttransplant anemia with histopathological characteristics of time-zero allograft biopsy and donor clinical characteristics. Methods We conducted a retrospective, observational cohort study that included 587 patients who underwent kidney transplantation in our Centre. Hemoglobin levels were assessed at 6 and 12 months after transplantation, and anemia was defined according to World Health Organization criteria. The kidney allograft time-zero biopsy has been done in all investigated cases. The evaluated histopathological parameters of the kidney allografts included glomerulosclerosis, arteriolar hyalinosis, vascular fibrous intimal thickening, interstitial fibrosis, tubular atrophy, and interstitial fibrosis and tubular atrophy. The Banff Classification of Allograft Pathology criteria were followed to assess the allograft histopathological changes. Results The prevalence of anemia was 31.3% at 6 months after transplantation and 23.5% at 12 months. There was an association between 20-50% glomerulosclerosis and posttransplant anemia in both time points, independently from eGFR. Arteriolar hyalinosis and interstitial fibrosis were identified as independent risk factors for anemia at 6 months after transplantation. Conclusion Histopathological features of time-zero kidney biopsy may be predictors of PTA. Among them, our study recognized 20-50% degree of glomerulosclerosis, AH, and CV as the most significant risk factors for PTA

An Exceptional Cause of Progressive Dyspnoea in a Renal Transplant Recipient: Hemangioma of the Mitral Valve

Primary cardiac hemangioma is a very rare benign vascular tumor, with valvular hemangiomas being even less frequent as valves are generally avascular structures. We present the first case of mitral valve hemangioma in a renal transplant recipient. Patient presented with progressive dyspnea. Transesophageal echocardiogram (TEE) demonstrated a 0.8x0.9-cm pedunculated tumor mass on the posterior leaflet of the mitral valve. Coronary angiography identified a small artery which filled from the circumflex artery and fed the tumor. The tumor was surgically removed. Histopathological examination revealed a hemangioma. The postoperative course was uneventful with stable graft function