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Background: BK polyomavirus associated nephropathy (BKPyVAN) is a significant clinical issue in kidney transplant (KT) recipients. No specific therapy is currently available, although treatment with leflunomide may be part of the therapeutic strategy. Here, we sought to examine the impact of leflunomide on the evolution of BKPyVAN., Methods: This was an observational retrospective study conducted in 3 French transplant centers. KT recipients who developed BKPyVAN and received leflunomide after failure of other treatment approaches were deemed eligible. Graft function, viral clearance, patient survival, rejection rates, treatment tolerability, and immunosuppression levels served as the main outcome measures., Results: A total of 55 patients were included. Treatment with leflunomide was started after a mean of 1.4 ± 4.1months  after BKPyVAN diagnosis. Between the introduction of leflunomide and the end of follow-up, creatinine levels increased by 31 ± 118% (P = 0.04), whereas viremia decreased by 79 ± 37% (P < 0.001). Blood viral clearance was observed in 76% of the study patients. Rejection episodes occurred in 33% of the participants. Eleven patients lost their graft (9 of which because of BKPyVAN). Ten patients developed adverse effects and 3 discontinued leflunomide., Conclusion: We cannot conclude about the exact place of leflunomide in the therapeutic strategy of BKPyVAN. It may be a part of the therapy to promote BK polyomavirus clearance in cases of BKPyVAN who fail to improve after immunosuppression lowering alone. Unfortunately, a significant decline in renal function and high rejection rates remain major clinical challenges., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

BK virus-associated nephropathy (BKVAN) causes renal allograft dysfunction. The current management of BKVAN relies on pre-emptive adaptation of immunosuppression according to viral load monitoring. However, this empiric strategy is not always successful. Therefore, pretransplant predictive markers are needed. In a prospective longitudinal study, we enrolled 168 kidney transplant recipients and 69 matched donors. To assess the value of BKV genotype-specific neutralizing antibody (NAb) titers as a predictive marker for BKV replication, we measured BKV DNA load and NAb titers at transplant and followed patients for 24 months. After transplant, 52 (31%) patients displayed BKV replication: 24 (46%) patients were viruric and 28 (54%) patients were viremic, including 13 with biopsy-confirmed BKVAN. At any time, patients with high NAb titers against the replicating strain had a lower risk of developing BKV viremia (hazard ratio [HR], 0.44; 95% confidence interval [95% CI], 0.26 to 0.73; P =0.002). Each log 10 increase in NAb titer decreased the risk of developing viremia by 56%. Replicating strains were consistent with donor transmission in 95% of cases of early BKV replication. Genotype mismatch between recipients' neutralization profiles before transplant and their subsequently replicating strain significantly increased the risk of developing viremia (HR, 2.27; 95% CI, 1.06 to 4.88; P =0.04). A NAb titer against the donor's strain <4 log 10 before transplant significantly associated with BKV replication after transplant (HR, 1.88; 95% CI, 1.06 to 3.45; P =0.03). BKV genotype-specific NAb titers may be a meaningful predictive marker that allows patient stratification by BKV disease risk before and after transplant., (Copyright © 2018 by the American Society of Nephrology.)

Background: Radiographic contrast media exposition can cause acute renal function impairment. There is limited and conflicting evidence that hydration with sodium bicarbonate prevents contrast-induced nephropathy (CIN) in patients undergoing cardiac catheterization., Objective: The present study was aimed at determining whether sodium bicarbonate is superior to hydration with saline to prevent nephropathy in patients at risk undergoing cardiac catheterization., Methods: Three hundred and one patients undergoing coronary angiography or percutaneous coronary intervention with serum creatinine > 1.2mg/dL or glomerular filtration rate (GFR) < 50 ml/min were randomized to receive hydration with sodium bicarbonate starting 1 hour before the procedure and 6 hours after the procedure, or hydration with 0.9% saline. CIN was defined as an increase of 0.5mg/dL in creatinine in 48 h, Results: Eighteen patients (5.9%) developed contrast induced nephropathy: 9 patients in the bicarbonate group (6.1%) and 9 patients in the saline group (6.0%), p = 0.97. The change in serum creatinine was similar in both groups, 0.01 ± 0.26 mg/dL in the bicarbonate group and 0.01 ± 0.35 mg/dL in the saline group, p = 0.9. No statistical difference was observed between the change in glomerular filtration rate (0.89 ± 9 ml/min vs. 2.29 ± 10 ml/min, p = 0.2 bicarbonate group and saline group, respectively)., Conclusion: Hydration with sodium bicarbonate was not superior to saline to prevent contrast media induced nephropathy in patients at risk undergoing cardiac catheterization.

Background: Although several risk factors associated with complications after renal biopsy (RB) have been identified, recommendations for RB procedures are still lacking. Our working group, appointed by the scientific commission of the Société de néphrologie in France, aimed to depict the main aspects of the practice of RB in adults in France, before establishing some guidelines., Methods: Members of the Société de néphrologie in France were asked to participate to 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 centers) 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 less than ten per year. Transjugular RB 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 hemorrhagic risk factors, care of patients with antiplatelet agents and hemorrhagic risk factors, and radiological guidance. Early discharge (<12 hours) was the rule in three (4.1%) units for native kidney biopsies and in ten (28.6%) units for graft biopsies., Conclusions: Our study is the first to provide a representative picture of "everyday" RB practices in a country. Consensual recommendations on all points mentioned are provided here., (Copyright © 2012. Published by Elsevier SAS.)

Retrospective studies suggest that chronic allograft nephropathy might progress more rapidly in patients with post-transplant anemia, but whether correction of anemia improves renal outcomes is unknown. An open-label, multicenter, randomized controlled trial investigated the effect of epoetin-β to normalize hemoglobin values (13.0-15.0 g/dl, n=63) compared with partial correction of anemia (10.5-11.5 g/dl, n=62) on progression of nephropathy in transplant recipients with hemoglobin <11.5 g/dl and an estimated creatinine clearance (eCrCl) <50 ml/min per 1.73 m(2). After 2 years, the mean hemoglobin was 12.9 and 11.3 g/dl in the normalization and partial correction groups, respectively (P<0.001). From baseline to year 2, the eCrCl decreased by a mean 2.4 ml/min per 1.73 m(2) in the normalization group compared with 5.9 ml/min per 1.73 m(2) in the partial correction group (P=0.03). Furthermore, fewer patients in the normalization group progressed to ESRD (3 versus 13, P<0.01). Cumulative death-censored graft survival was 95% and 80% in the normalization and partial correction groups, respectively (P<0.01). Complete correction was associated with a significant improvement in quality of life at 6 and 12 months. The number of cardiovascular events was low and similar between groups. In conclusion, this prospective study suggests that targeting hemoglobin values ≥13 g/dl reduces progression of chronic allograft nephropathy in kidney transplant recipients.

Background and Objectives: Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy with a wide spectrum of clinical features including obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal abnormalities. The molecular genetic profile of BBS is currently being investigated after the recent identification of 14 BBS genes involved in primary cilia-linked disease. This study aims to characterize the renal and cardiovascular presentations and to analyze possible relationships between genotypes and clinical phenotypes., Design, Setting, Participants & Measurements: This clinical study was performed in a national cohort of 33 BBS patients, 22 men and 11 women, all aged >16 years (mean age 26.3 years)., Results: Renal abnormalities, including impairment of renal function and signs of chronic interstitial nephropathy of dysplastic nature, were documented in 82% of the patients. Cardiovascular evaluations revealed that this group of young patients had significant cardiovascular risk factors. Hypertension was found in >30% of the patients and hyperlipidemia in >60%, and almost 50% had other metabolic abnormalities. Overt diabetes was present in only 6%. With regard to genotype-phenotype correlation, patients with a mutation in the BBS6, BBS10, or BBS12 gene (10 of 33 patients) had more severe renal disease., Conclusions: Our study results confirm the frequent occurrence of renal involvement in patients with BBS, underscore the high risk of cardiovascular disease in these patients, and provide new information on a possible genotype-phenotype correlation.

Background and Objectives: Sarcoidosis is a multisystem disorder of unknown etiology. The outcome of renal transplantation on patients with sarcoidosis is not well known. A few case reports have described recurrence of sarcoidosis after transplant. Here, we report for the first time results and outcome of renal transplantation in a series of patients with sarcoidosis., Design, Setting, Participants, & Measurements: Eighteen patients with sarcoidosis who underwent renal transplantation were identified retrospectively in eight French renal transplantation departments. Patient medical charts, demographics, and the outcome of renal transplantation were reviewed., Results: Initial renal disease was related to sarcoidosis in 10 patients. At the end of the follow-up (median, 42 months), patient and death-censored graft survival were 94.4% and the mean GFR was 60 ml/min per 1.73 m(2). Five patients (27%) experienced recurrence of sarcoidosis including extra-renal involvement in two patients and renal involvement in three patients. Median GFR was lower in the group of patients with renal recurrence compared with that of the entire cohort: 31 ml/min per 1.73 m(2). Recurrence occurred shortly after transplantation (median period, 13 months). Risk factors for recurrence included primary renal disease related to sarcoidosis and a shorter delay between the last episode of sarcoidosis and renal transplantation., Conclusions: Our results indicate that renal transplantation may be carried out safely in transplant candidates with sarcoidosis. Recurrence is not rare and is likely to affect graft outcome. These results fully justify a specific clinical and histologic monitoring mainly during the early posttransplant period.

Parathyroid hormone-related protein (PTHrP) belongs to vasoactive factors that regulate blood pressure and renal hemodynamics both by reducing vascular tone and raising renin release. PTHrP is expressed in systemic and renal vasculature. Here, we wanted to assess the contribution of vascular smooth muscle cell endogenous PTHrP to the regulation of cardiovascular and renal functions. We generated a mouse strain (SMA-CreERT2/PTHrPL2/L2 or premutant PTHrPSM-/-), which allows temporally controlled, smooth muscle-targeted PTHrP knockdown in adult mice. Tamoxifen treatment induced efficient recombination of PTHrP-floxed alleles and decreased PTHrP expression in vascular and visceral smooth muscle cells of PTHrPSM-/- mice. Blood pressure remained unchanged in PTHrPSM-/- mice, but plasma renin concentration and creatinine clearance were reduced. Renal hemodynamics were further analyzed during clearance measurements in anesthetized mice. Conditional knockdown of PTHrP decreased renal plasma flow and glomerular filtration rate with concomitant reduction in filtration fraction. Similar measurements were repeated during acute saline volume expansion. Saline volume expansion induced a rise in renal plasma flow and reduced filtration fraction; both were blunted in PTHrPSM-/- mice leading to impaired diuresis. These findings show that endogenous vascular smooth muscle PTHrP controls renal hemodynamics under basal conditions, and it is an essential factor in renal vasodilation elicited by saline volume expansion. [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]

Studies of the primary cilium, now known to be present in all cells, have undergone a revolution, in part, because mutation of many of its proteins causes a large number of diseases, including cystic kidney disease. Bardet-Biedl syndrome (BBS) is an inherited ciliopathy characterized, among other dysfunctions, by renal defects for which the precise role of the cilia in kidney function remains unclear. We studied a cohort of patients with BBS where we found that these patients had a urinary concentration defect even when kidney function was near normal and in the absence of major cyst formation. Subsequent in vitro analysis showed that renal cells in which a BBS gene was knocked down were unciliated, but did not exhibit cell cycle defects. As the vasopressin receptor 2 is located in the primary cilium, we studied BBS-derived unciliated renal epithelial cells and found that they were unable to respond to luminal arginine vasopressin treatment and activate their luminal aquaporin 2. The ability to reabsorb water was restored by treating these unciliated renal epithelial cells with forskolin, a receptor-independent adenylate cyclase activator, showing that the intracellular machinery for water absorption was present but not activated. These findings suggest that the luminal receptor located on the primary cilium may be important for efficient transepithelial water absorption. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine whether low platelet response to the P2Y12 receptor antagonist clopidogrel as assessed by vasodilator-stimulated phosphoprotein flow cytometry test (VASP-FCT) differentially affects outcomes in patients with or without chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). Background: Although both CKD and impaired platelet responsiveness to clopidogrel are strong predictors of unfavorable outcome after PCI, the impact of their association is unknown. The platelet VASP-FCT assay is specific for the P2Y12 ADP receptor pathway. In this test, platelet activation is expressed as the platelet reactivity index (PRI). Methods: Four-hundred forty unselected patients (CKD: 126, estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2), no-CKD: 314 eGFR >60 ml/min/1.73 m2) undergoing urgent (n = 336) or planned (n = 104) PCI were prospectively enrolled. In each subgroup, patients were classified as low-responders (LR: PRI ≥61%) or responders (R: PRI <61%) to clopidogrel. Results: At a mean follow-up of 9 ± 2 months, all-cause mortality, cardiac death, and possible stent thrombosis were higher in CKD than in no-CKD patients. Within the CKD group, the LR status was associated with higher rates of all-cause mortality (25.5% vs. 2.8%, p < 0.001), cardiac death (23.5% vs. 2.8%, p < 0.001), all stent thrombosis (19.6% vs. 2.7%, p = 0.003), and MACE (33.3% vs. 12.3%, p = 0.007). Conversely, in no-CKD patients, the LR status did not affect outcomes. Multivariate analysis identified Killip class ≥3, drug-eluting stent implantation, and the interaction between LR and CKD (hazard ratio: 11.96, 95% confidence interval: 1.22 to 116.82; p = 0.033) as independent predictors of cardiac death. Conclusions: In CKD patients, the presence of low platelet response to clopidogrel is associated with worse outcomes after PCI. [ABSTRACT FROM AUTHOR]