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Background Primary hyperoxalurias (PH) are extremely rare genetic disorders characterized by clinical heterogeneity. Delay in diagnosing these conditions can have detrimental effects on patient outcomes. The primary objective of this study is to assess the current diagnostic delay for PH. Methods This nationwide, observational and retrospective study included patients who received a genetic diagnosis of PH types 1, 2 and 3 between 1 January 2015 and 31 December 2019. Diagnostic delay was defined as the duration between the onset of symptoms and the time of genetic diagnosis. Results A total of 52 patients (34 children and 18 adults) were included in the study, with 40 PH1 (77%), 3 PH2 (6%) and 9 PH3 (17%). At the time of diagnosis, 12 patients (23%) required dialysis. Among the PH1 patients, the predominant symptom at onset in adults was renal colic (79% of cases), whereas symptoms in children were more diverse (renal colic in 17% of cases). The diagnostic delay was significantly shorter in children compared with adults [median (interquartile range)]: 1.2 (0.1–3.0) versus 30 (17–36) years, respectively (P  < .0001). RNA interference was utilized in 23 patients (58%). Five individuals (13%) underwent double liver–kidney transplantation, and five (13%) received isolated kidney transplantation, with lumasiran therapy in four patients. For PH2 and PH3 patients, the diagnostic delay ranges from 0 to 3 years, with renal colic as first symptom in 33% of cases. Conclusion This extensive and recent cohort of PH underscores the considerable delay in diagnosing PH, particularly in adults, even in a country with a dedicated organization for enhancing the overall management of rare diseases. These findings reinforce the imperative for increased awareness among relevant specialties regarding the evaluation of urolithiasis. [ABSTRACT FROM AUTHOR]

Early post-transplant recurrence of oxalate nephropathy in a patient with primary hyperoxaluria type 1, despite pretransplant lumasiran therapy. That being said, the B6 sensitivity was difficult to assess in Patients 1 and 3 since PH1 was diagnosed at the time of kidney failure, and in Patient 5, despite maximal B6 therapy at the time of conservative therapy, an important hyperoxaluria remained. Among patients who reach kidney failure, intensive hemodialysis should be performed; however, systemic oxalosis worsens despite intensive dialysis, and bone is the main compartment for oxalate storage. However, the proposed thresholds of POx for a safe transplant procedure, namely around 20 µmol/L [[13]], appear quite optimistic and probably not attainable in most patients, keeping in mind the POx levels observed in dialysis in non-PH1 patients. [Extracted from the article]

Background: Recent years have seen increasing use of rituximab (RTX) for various types of primary and secondary glomerulopathies. However, there are no studies that specifically address the risk of infection related to this agent in patients with these conditions. Methods: We reviewed the outcomes of all patients who received RTX therapy for glomerular disease between June 2000 and October 2011 in eight French nephrology departments. Each case was analysed for survival, cause of death if a non-survivor and/or the presence of infectious complications, including severe or opportunistic infection occurring within the 12 months following RTX infusion. Results: Among 98 patients treated with RTX, 25 presented with at least one infection. We report an infection rate of 21.6 per 100 patient-years. Five patients died within 12 months following an RTX infusion, of whom four also presented with an infection. The median interval between the last RTX infusion and the first infectious episode was 2.1 months (interquartile range 0.5-5.1). Most infections were bacterial (79%) and pneumonia was the most frequent infection reported (27%). The presence of diabetes mellitus (P = 0.006), the cumulative RTX dose (P = 0.01) and the concomitant use of azathioprine (P = 0.03) were identified as independent risk factors. Renal failure was significantly associated with an increased infection risk by bivariate analysis (P = 0.03) and was almost significant by multivariate analysis (P = 0.05). Nephrotic syndrome did not further increase the risk of infection and/or death. Conclusion: The risk of infection after RTX-based immunosuppression among patients with glomerulopathy must be considered and patients should receive close monitoring and appropriate infection prophylaxis, especially in those with diabetes and high-dose RTX regimens. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) represent an increasing proportion of the population undergoing percutaneous coronary intervention (PCI) and up to 40% of the patients treated for acute coronary syndrome (ACS). Several studies and registries in the setting of ACS and elective PCI have reported a negative association between CKD and mortality, stent thrombosis, post-procedural ischaemic events and bleeding events. Pharmacological inhibition of the adenosine diphosphate receptor by thienopyridines or ticagrelor and disruption of the cyclooxygenase pathway by aspirin constitute the current standards of care to prevent thrombotic complications following stent-based PCI. In CKD patients, the avoidance of anti-platelet therapy may be driven by the lack of clinical trial data to support its efficacy, by errors or omissions, or by a reluctance to use this therapy in a population characterized by its enhanced bleeding risk. However, there is growing evidence to suggest that a severely decreased glomerular filtration rate per se, independent of the presence of diabetes mellitus, is an important determinant of high residual platelet reactivity under a clopidogrel maintenance dose. Recent reports have emphasized that the impact of impaired platelet inhibition by thienopyridines is of paramount importance in CKD patients, with an enhanced mortality rate in low-responder patients. Pharmacodynamic studies indicate the phosphodiesterase 3 inhibitor, cilostazol, the third generation thienopyridine prasugrel and the reversible P2Y12 antagonist ticagrelor to be potent strategies to overcome this biological resistance. In clinical practice, platelet function testing should be considered in CKD patients undergoing PCI, especially in those who experience thrombotic events despite dual therapy. Newer agents should be contemplated in patients who display higher residual platelet aggregability after standard treatment. Among these, the non-thienopyridine P2Y12 receptor antagonist ticagrelor, which does not require biotransformation, could be the drug of choice in CKD patients with ACS. In this population, ticagrelor has been found to reduce mortality and ischaemic events with an acceptable bleeding risk. [ABSTRACT FROM AUTHOR]

Background Short-term intensified dosing using enteric-coated mycophenolate sodium (EC-MPS) reduces rejection after kidney transplantation without compromising safety and may facilitate steroid avoidance. Methods In a 6-month, multicentre open-label trial, 222 de novo kidney transplant recipients at low-immunological risk were randomized to steroid avoidance or maintenance steroids with interleukin (IL)-2 receptor antibody (IL-2RA) induction, EC-MPS (2160 mg/day to Week 6, 1440 mg/day thereafter) and cyclosporine. Results The primary end point; treatment failure at Month 6 [biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up], occurred in 17.9% (20/112) of steroid-avoidance patients and 14.5% (16/110) of controls (difference 3.4%, 95% confidence interval −6.3 to 13.1, P = 0.47 for superiority testing). BPAR occurred in 11.6 and 7.3% of patients in the steroid-avoidance and control arms, respectively (P = 0.27). Creatinine clearance was similar at Month 6 (steroid-avoidance 56 ± 18 mL/min/1.73m2, controls 60 ± 22 mL/min/1.73m2, P = 0.34). Cytomegalovirus infection, as reported by investigators, occurred in 12.5% of steroid-avoidance patients and 22.7% of controls (P = 0.045). Conclusions A regimen of early intensified EC-MPS dosing with calcineurin inhibitor and IL-2RA induction permits oral steroid avoidance in adult kidney transplant patients at low-immunological risk without compromising efficacy at 6 months' follow-up. [ABSTRACT FROM PUBLISHER]

Background. Although several risk factors associated with complications after renal biopsy (RB) have been identified, the gold standard for RB procedures remains to be defined. Practices vary widely among nephrologists, depending on personal experience and the availability of particular techniques. The purpose of our study was to depict the main aspects of the practice of RB in adults in France.Methods. Members of the Société de Néphrologie in France were asked to participate in a questionnaire survey on RB procedures.Results. Eighty-eight nephrologists from 74 units (27 in teaching hospitals, 35 in public general hospitals and 12 in private centres) participated in our study. Native kidney and graft biopsies were performed in 73 and 35 units, respectively. RB activity was highly variable among units, ranging from several hundred to <10 per year. Transjugular renal biopsy was judged to be smoothly accessible in 28 out of 73 units (38.4%). Significant variations in practices were observed regarding patient information before RB, assessment of haemorrhagic risk factors, management of patients with antiplatelet agents and haemorrhagic risk factors, and radiological guidance. Early discharge (<12 h) was the rule in 3 (4.1%) units for native kidney biopsies and in 10 (28.6%) units for graft biopsies.Conclusions. Our study is the first to provide a representative picture of ‘everyday’ RB practices in a country. Important variations in procedures were observed. Our study may represent a preliminary step for the elaboration of guidelines for all aspects of RB practices. [ABSTRACT FROM AUTHOR]

Background. Hypertension is a risk factor for the two leading causes of death in renal transplant recipients: cardiovascular disease (CVD) and graft failure. Despite this, the optimum medication for post-transplant hypertension is unclear. [ABSTRACT FROM PUBLISHER]

Background. Among hereditary fevers characterized by recurrent attacks of fever and organ localized inflammation, familial Mediterranean fever (FMF), and tumour necrosis factor receptor superfamily 1A (TNFRSF1A) receptor associated periodic syndrome (TRAPS) are diseases with identified genes that can be associated with renal amyloidosis of the AA type. In this study we have characterized FMF and TRAPS genotypes in 38 unrelated patients suffering from amyloidosis AA and recurrent inflammatory attacks. [ABSTRACT FROM PUBLISHER]