Description of a multidisciplinary model of care in a French cohort of adult patients with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Due to the various manifestations of TSC and their potential complications, a multidisciplinary care approach is recommended by consensus guidelines. OBJECTIVES: Our study aimed to give a complete description of our TSC adult cohort and to evaluate the multidisciplinary and interdisciplinary management model. METHODS: Data on each adult patient diagnosed with TSC, including disease manifestations, interventions and outcomes, were collected at baseline and updated annually. A multidisciplinary TSC approach with all the recommended explorations was carried out annually. RESULTS: 90 patients were enrolled in Centre Hospitalier Universitaire de Bordeaux, between January 2000 and September 2018. Median age of patients at inclusion was 37 years (range, 27-47) and 20 years old at diagnosis of TSC. Regarding the occurrence of TSC manifestations, 97% of the patients had cutaneous lesions, 89% had neurological manifestations, 83% had renal manifestations and 100% had dental lesions with pits. More than half the patients had sclerotic bone lesions (68%), TSC-associated neuropsychiatric disorders (64%) and lymphangioleiomyomatosis (59%). A TSC multidisciplinary approach was developed including a global follow-up and an evaluation of TSC targeting organs, according to the recommendations. A satisfaction survey revealed global and entire satisfaction of patients with TSC. CONCLUSION: We obtained an accurate description of a cohort of adult patients with TSC. Our multidisciplinary approach model allowed us to provide optimal management of patients with TSC with a high level of patient satisfaction.

Vascularization of Cell-Laden Microfibres by Femtosecond Laser Processing.

To face the increasing demand for organ transplantation, currently the development of tissue engineering appears as the best opportunity to effectively regenerate functional tissues and organs. However, these approaches still face the lack of an efficient method to produce an efficient vascularization system. To answer these issues, the formation of an intra-volume channel within a three-dimensional, scaffold free, mature, and cell-covered collagen microfibre is here investigated through laser-induced cavitation. An intra-volume channel was formed upon irradiation with a near-infrared, femtosecond laser beam, focused with a high numerical aperture lens. The laser beam directly crossed the surface of a dense and living-cell bilayer and was focused behind the bilayer to induce channel formation in the hydrogel core while preserving the cell bilayer. Channel formation was assessed through confocal microscopy. Channel generation inside the hydrogel core was enhanced by the formation of voluminous cavitation bubbles with a lifetime longer than 30 s, which also improved intra-volume channel durability. Twenty-four hours after laser processing, cellular viability dropped due to a lack of sufficient hydration for processing longer than 10 min. However, the processing automation could drastically reduce the cellular mortality, this way enabling the formation of hollowed microfibres with a high density of living-cell outer bilayer.

Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy.

Primary membranous nephropathy (MN) is an autoimmune glomerular disease in which autoantibodies are directed against podocyte proteins. In about 80% of cases the main targeted antigen is the phospholipase A2 receptor 1 (PLA2R1). Anti-PLA2R1 antibodies are mainly immunoglobulin G type 4 (IgG4). However, the antigenic target remains to be defined in 20% of cases. MN can be associated with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system where a common antigenic target has yet to be identified. To ascertain a possible novel target antigen, we analyzed kidney biopsies from five patients positive for anti-contactin 1 antibodies and presenting with MN combined with chronic inflammatory demyelinating polyneuropathy. Eluted IgG from biopsy sections against contactin 1 and nerve tissue were screened. Western blot revealed contactin 1 expression in normal kidney glomeruli. Confocal microscopic analysis showed the presence and colocalization of contactin 1 and IgG4 on the glomerular basement membrane of these patients. Glomerular contactin 1 was absent in patients with anti-PLA2R1-associated MN or membranous lupus nephritis or a healthy control. The eluted IgG from contactin 1-positive biopsy sections but not the IgG eluted from patients with PLA2R1 MN bound contactin 1 with the main eluted subclass IgG4. Eluted IgG could bind paranodal tissue (myelinated axon) and colocalized with commercial anti-contactin 1 antibody. Thus, contactin 1 is a novel common antigenic target in MN associated with chronic inflammatory demyelinating polyneuropathy. However, the precise pathophysiology remains to be elucidated.

Incidence, prognostic impact and clinical outcomes of renal impairment in patients with multiple myeloma: a population-based registry.

BACKGROUND: Renal impairment (RI), a severe complication in multiple myeloma (MM), is considered as a poor prognostic factor. Patient survival has increased with the use of novel drugs and autologous stem-cell transplantation (ASCT). However, specific evolution of the incidence of RI in MM and its impact on prognosis remain unclear. METHODS: Using a population-based registry of 1038 newly diagnosed MM in Gironde, France, we evaluated the incidence trends of RI in MM patients and assessed net survival according to factors of interest using Pohar-Perme indicator and excess mortality rate regression. We also reviewed 114 cases of MM with RI to describe their clinical outcomes. RESULTS: In our population-based study, 24.6% of MM patients presented with RI (12.9% required haemodialysis). Median survival time was 21 months in patients with RI versus not reached at 3 years for other patients (P < 0.01). Age >73 years, RI, comorbidities and non-use of drugs or ASCT were associated with excess mortality risk. The effect of RI on excess mortality rates was maximum in the first 6 months after diagnosis. In the observational study, median follow-up time was 22.5 months; factors associated with renal response were haematologic response [odds ratio (OR) 6.81; P < 0.01] and previous chronic kidney disease (OR 0.26; P = 0.04). Factors associated with 1-year overall survival were haematological [hazard ratio (HR) 0.13; P < 0.01] and renal response (HR 0.27; P = 0.03). CONCLUSIONS: RI represents an independent negative prognostic factor in MM in the first 6 months after diagnosis. Renal recovery and haematologic response are the strongest markers associated with patient survival.

Intra-volume processing of gelatine hydrogel by femtosecond laser-induced cavitation.

Cell oxygenation and nutrition are crucial for the viability of tissue-engineered constructs, and different alternatives are currently being developed to achieve an adequate vascularisation of the engineered tissue. One of the alternatives is the generation of channel-like patterns in a bioconstruct. Here, the formation of full-formed channels inside hydrogels by laser-induced cavitation was investigated. A near-infrared, femtosecond laser beam focused with a high numerical aperture was employed to obtain intra-volume modifications of a block of gelatine hydrogel. Characterisation of the laser-processed gelatine was carried out by optical microscopy and epifluorescence microscopy right after and 24 h after the laser process. Rheology analyses on the unprocessed gelatine blocks were conducted to better understand the cavitation mechanism taking place during the intense laser interaction. Different cavitation patterns were observed at varying dose values by changing the repetition rate and the overlap between successive pulses while keeping the laser fluence and the number of passes fixed. This way, cavitation bubble features and behaviour can be controlled to optimise the formation of intra-volume channels in the gelatine volume. Results showed that the generation of fully formed channels was linked to the formation of large non-spherical cavitation bubbles during the laser interaction at high dose and low repetition rates. In conclusion, the formation of fully formed channels was made possible with a near-infrared, femtosecond laser beam strongly focused inside gelatine hydrogel blocks through laser-induced cavitation at high dose and low repetition rates.

Chronic interstitial nephritis in agricultural communities is a toxin-induced proximal tubular nephropathy.

Almost 30 years after the detection of chronic interstitial nephritis in agricultural communities (CINAC) its etiology remains unknown. To help define this we examined 34 renal biopsies from Sri Lanka, El Salvador, India and France of patients with chronic kidney disease 2-3 and diagnosed with CINAC by light and electron microscopy. In addition to known histopathology, we identified a unique constellation of proximal tubular cell findings including large dysmorphic lysosomes with a light-medium electron-dense matrix containing dispersed dark electron-dense non-membrane bound "aggregates". These aggregates associated with varying degrees of cellular/tubular atrophy, apparent cell fragment shedding and no-weak proximal tubular cell proliferative capacity. Identical lysosomal lesions, identifiable by electron microscopy, were observed in 9% of renal transplant implantation biopsies, but were more prevalent in six month (50%) and 12 month (67%) protocol biopsies and in indication biopsies (76%) of calcineurin inhibitor treated transplant patients. The phenotype was also found associated with nephrotoxic drugs (lomustine, clomiphene, lithium, cocaine) and in some patients with light chain tubulopathy, all conditions that can be directly or indirectly linked to calcineurin pathway inhibition or modulation. One hundred biopsies of normal kidneys, drug/toxin induced nephropathies, and overt proteinuric patients of different etiologies to some extent could demonstrate the light microscopic proximal tubular cell changes, but rarely the electron microscopic lysosomal features. Rats treated with the calcineurin inhibitor cyclosporine for four weeks developed similar proximal tubular cell lysosomal alterations, which were absent in a dehydration group. Overall, the finding of an identical proximal tubular cell (lysosomal) lesion in CINAC and calcineurin inhibitor nephrotoxicity in different geographic regions suggests a common paradigm where CINAC patients undergo a tubulotoxic mechanism similar to calcineurin inhibitor nephrotoxicity.

Adult onset tubulo-interstitial nephropathy in MT-ND5-related phenotypes.

Kidney is a highly adenosine triphosphate dependent organ in human body. Healthy and functional mitochondria are essential for normal kidney function. Clinical and genetic variability are the hallmarks of mitochondrial disorders. We report here the involvement of two MT-ND5 pathogenic variants encoding for ND5 subunit of respiratory chain complex I, the m.13513G>A and the m.13514A>G, in adult-onset kidney disease in three unrelated patients. The first patient had myopathy encephalopathy lactic acidosis and stroke syndrome, left ventricular hypertrophy with Wolff-Parkinson-White syndrome and tubulo-interstitial kidney disease. The second presented Leber hereditary optic neuropathy associated with tubulo-interstitial kidney disease. The third presented with an isolated chronic tubulo-interstitial kidney disease. These mutations have never been associated with adulthood mitochondrial nephropathy. These case reports highlight the importance to consider mitochondrial dysfunction in tubulo-interstitial kidney disease.

Towards an in vitro model of the glomerular barrier unit with an innovative bioassembly method.

BACKGROUND: The development of an artificial glomerular unit may be pivotal for renal pathophysiology studies at a multicellular scale. Using a tissue engineering approach, we aimed to reproduce in part the specific glomerular barrier architecture by manufacturing a glomerular microfibre (Mf). METHODS: Immortalized human glomerular cell lines of endothelial cells (GEnCs) and podocytes were used. Cells and a three-dimensional (3D) matrix were characterized by immunofluorescence with confocal analysis, Western blot and polymerase chain reaction. Optical and electron microscopy were used to study Mf and cell shapes. We also analysed cell viability and cell metabolism within the 3D construct at 14 days. RESULTS: Using the Mf manufacturing method, we repeatedly obtained a cellularized Mf sorting human glomerular cells in 3D. Around a central structure made of collagen I, we obtained an internal layer composed of GEnC, a newly formed glomerular basement membrane rich in α5 collagen IV and an external layer of podocytes. The cell concentration, optimal seeding time and role of physical stresses were modulated to obtain the Mf. Cell viability and expression of specific proteins (nephrin, synaptopodin, vascular endothelial growth factor receptor 2 (VEGFR2) and von Willebrandt factor (vWF)) were maintained for 19 days in the Mf system. Mf ultrastructure, observed with EM, had similarities with the human glomerular barrier. CONCLUSION: In summary, with our 3D bio-engineered glomerular fibre, GEnC and podocytes produced a glomerular basement membrane. In the future, this glomerular Mf will allow us to study cell interactions in a 3D system and increase our knowledge of glomerular pathophysiology.

CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine.

Inflammation is a major contributor to tubular epithelium injury in kidney disorders, and the involvement of blood platelets in driving inflammation is increasingly stressed. CD154, the ligand of CD40, is one of the mediators supporting platelet proinflammatory properties. Although hypoxia is an essential constituent of the inflammatory reaction, if and how platelets and CD154 regulate inflammation in hypoxic conditions remain unclear. Here, we studied the control by CD154 of the proinflammatory cytokine interleukin- (IL-) 6 secretion in short-term oxygen (O2) deprivation conditions, using the HK-2 cell line as a kidney tubular epithelial cell (TEC) model. IL-6 secretion was markedly stimulated by CD154 after 1 to 3 hours of hypoxic stress. Both intracellular IL-6 expression and secretion were stimulated by CD154 and associated with a strong upregulation of IL-6 mRNA and increased transcription. Searching for inhibitors of CD154-mediated IL-6 production by HK-2 cells in hypoxic conditions, we observed that chloroquine, a drug that has been repurposed as an anti-inflammatory agent, alleviated this induction. Therefore, CD154 is a potent early stimulus for IL-6 secretion by TECs in O2 deprivation conditions, a mechanism likely to take part in the deleterious inflammatory consequences of platelet activation in kidney tubular injury. The inhibition of CD154-induced IL-6 production by chloroquine suggests the potential usefulness of this drug as a therapeutic adjunct in conditions associated with acute kidney injury.

An open-label randomized controlled trial of low-dose corticosteroid plus enteric-coated mycophenolate sodium versus standard corticosteroid treatment for minimal change nephrotic syndrome in adults (MSN Study).

First-line therapy of minimal change nephrotic syndrome (MCNS) in adults is extrapolated largely from pediatric studies and consists of high-dose oral corticosteroids. We assessed whether a low corticosteroid dose combined with mycophenolate sodium was superior to a standard oral corticosteroid regimen. We enrolled 116 adults with MCNS in an open-label randomized controlled trial involving 32 French centers. Participants randomly assigned to the test group (n=58) received low-dose prednisone (0.5 mg/kg/day, maximum 40 mg/day) plus enteric-coated mycophenolate sodium 720 mg twice daily for 24 weeks; those who did not achieve complete remission after week 8 were eligible for a second-line regimen (increase in the prednisone dose to 1 mg/kg/day with or without Cyclosporine). Participants randomly assigned to the control group (n=58) received conventional high-dose prednisone (1 mg/kg/day, maximum 80 mg/day) for 24 weeks. The primary endpoint of complete remission after four weeks of treatment was ascertained in 109 participants, with no significant difference between the test and control groups. Secondary outcomes, including remission after 8 and 24 weeks of treatment, did not differ between the two groups. During 52 weeks of follow-up, MCNS relapsed in 15 participants (23.1%) who had achieved the primary outcome. Median time to relapse was similar in the test and control groups (7.1 and 5.1 months, respectively), as was the incidence of serious adverse events. Five participants died from hemorrhage (n=2) or septic shock (n=3), including 2 participants in the test group and 3 in the control group. Thus, in adult patients, treatment with low-dose prednisone plus enteric-coated mycophenolate sodium was not superior to a standard high-dose prednisone regimen to induce complete remission of MCNS.

High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy.

Podocytes play a key role in diabetic nephropathy pathogenesis, but alteration of their metabolism remains unknown in human kidney. By using a conditionally differentiating human podocyte cell line, we addressed the functional and molecular changes in podocyte energetics during in vitro development or under high glucose conditions. In 5 mM glucose medium, we observed a stepwise activation of oxidative metabolism during cell differentiation that was characterized by peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)-dependent stimulation of mitochondrial biogenesis and function, with concomitant reduction of the glycolytic enzyme content. Conversely, when podocytes were cultured in high glucose (20 mM), stepwise oxidative phosphorylation biogenesis was aborted, and a glycolytic switch occurred, with consecutive lactic acidosis. Expression of the master regulators of oxidative metabolism transcription factor A mitochondrial, PGC-1α, AMPK, and serine-threonine liver kinase B1 was altered by high glucose, as well as their downstream signaling networks. Focused transcriptomics revealed that myocyte-specific enhancer factor 2C (MEF2C) and myogenic factor 5 (MYF5) expression was inhibited by high glucose levels, and endoribonuclease-prepared small interfering RNA-mediated combined inhibition of those transcription factors phenocopied the glycolytic shift that was observed in high glucose conditions. Accordingly, a reduced expression of MEF2C, MYF5, and PGC-1α was found in kidney tissue sections that were obtained from patients with diabetic nephropathy. These findings obtained in human samples demonstrate that MEF2C-MYF5-dependent bioenergetic dedifferentiation occurs in podocytes that are confronted with a high-glucose milieu.-Imasawa, T., Obre, E., Bellance, N., Lavie, J., Imasawa, T., Rigothier, C., Delmas, Y., Combe, C., Lacombe, D., Benard, G., Claverol, S., Bonneu, M., Rossignol, R. High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy.

Rhabdomyolysis after co-administration of a statin and fusidic acid: an analysis of the literature and of the WHO database of adverse drug reactions.

Following a severe case of rhabdomyolysis in our University Hospital after a co-administration of atorvastatin and fusidic acid, we describe this interaction as this combination is not clearly contraindicated in some countries, particularly for long-term treatment by fusidic acid. All cases of rhabdomyolysis during a co-administration of a statin and fusidic acid were identified in the literature and in the World and Health Organization database, VigiBase® . In the literature, 29 cases of rhabdomyolysis were identified; mean age was 66 years, median duration of co-administration before rhabdomyolysis occurrence was 21 days, 28% of cases were fatal. In the VigiBase® , 182 cases were retrieved; mean age was 68 years, median duration of co-administration before rhabdomyolysis was 31 days and 24% of cases were fatal. Owing to the high fatality associated with this co-administration and the long duration of treatment before rhabdomyolysis occurrence, fusidic acid should be used if there is no appropriate alternative, as long as statin therapy is interrupted for the duration of fusidic acid therapy, and perhaps a week longer. Rarely will interruption of this sort have adverse consequences for the patient.

CD154 Induces Matrix Metalloproteinase-9 Secretion in Human Podocytes.

Matrix remodeling is a key feature of glomerulosclerosis secondary to diabetes or hypertension. Podocytes contribute to glomerular basement membrane (GBM) turnover by producing matrix components and matrix remodelling enzymes, including matrix metalloproteinases (MMPs). The CD40/CD154 signaling pathway modulates matrix remodeling through the synthesis of MMPs and tissue inhibitors of MMPs. Platelets are a primary blood reservoir of CD154. Here we studied, the impact of the CD154/CD40 pathway on MMP-9 expression by cultured human podocytes. The role of CD40/CD154 was evaluated upon exposure of podocytes to recombinant human CD154 (rhCD154) or activated platelet supernatants from healthy human subjects. We first showed by protein and mRNA expression that CD40 was synthesized by podocytes and detectable on kidney tissue sections. CD40 expression was acquired during podocyte differentiation and enhanced upon exposure to rhCD154. In podocytes, rhCD154 induced an increase of MMP-9 production as shown by RT-PCR, Western blot and and gelatin zymography. Activated platelet supernatants induced MMP-9 mRNA synthesis in podocytes, an effect reduced by anti-CD40 antibody. Our results underscore a potential role for platelets through the CD40/CD154 signaling pathway in the control of GBM synthesis and degradation, via its regulatory role on MMP-9 production. CD154 secretion by activated platelets may contribute to GBM alterations in proteinuric nephropathies. J. Cell. Biochem. 117: 2737-2747, 2016. © 2016 Wiley Periodicals, Inc.

Con: Higher serum bicarbonate in dialysis patients is protective.

Metabolic acidosis is often observed in advanced chronic kidney disease, with deleterious consequences on the nutritional status, bone and mineral status, inflammation and mortality. Through clearance of the daily acid load and a net gain in alkaline buffers, dialysis therapy is aimed at correcting metabolic acidosis. A normal bicarbonate serum concentration is the recommended target in dialysis patients. However, several studies have shown that a mild degree of metabolic acidosis in patients treated with dialysis is associated with better nutritional status, higher protein intake and improved survival. Conversely, a high bicarbonate serum concentration is associated with poor nutritional status and lower survival. It is likely that mild acidosis results from a dietary acid load linked to animal protein intake. In contrast, a high bicarbonate concentration in patients treated with dialysis could result mainly from an insufficient dietary acid load, i.e. low protein intake. Therefore, a high pre-dialysis serum bicarbonate concentration should prompt nephrologists to carry out nutritional investigations to detect insufficient dietary protein intake. In any case, a high bicarbonate concentration should be neither a goal of dialysis therapy nor an index of adequate dialysis, whereas mild acidosis could be considered as an indicator of appropriate protein intake.

Distal Angiopathy and Atypical Hemolytic Uremic Syndrome: Clinical and Functional Properties of an Anti-Factor H IgAλ Antibody.

Abnormal regulation of the alternative pathway of the complement system is a well-described trigger of microangiopathy leading to atypical hemolytic uremic syndrome (aHUS). However, the involvement of complement dysregulation in distal angiopathy has not been reported in adults. We describe the clinical course of a patient with severe distal angiopathy (amputation of all fingers and toes) followed 3 years later by aHUS with end-stage renal disease. This course was attributed to a circulating monoclonal immunoglobulin A λ light chain (IgAλ) with unusual properties: it bound complement factor H (CFH) and impaired CFH-glycosaminoglycan interaction and cell-surface protection. Local complement activation with distal angiopathy and microvascular injury was suggested by deposition of IgA, C4d, and C5b-9 in limb and preglomerular arteries. We therefore postulated that the monoclonal IgAλ inhibited activity of endothelial cell-bound CFH, which led to local activation of complement, vasoconstriction (distal angiopathy), and aHUS. While the patient was dependent on dialysis and plasma exchange, treatment with the anti-C5 antibody eculizumab induced remission of distal angiopathy and aHUS. During eculizumab treatment, kidney transplantation was performed. The patient had normal kidney function at the 3-year follow-up. We suggest that the association of distal angiopathy and aHUS in this patient is clearly linked to anti-CFH properties of the monoclonal IgAλ.

Cytomegalovirus-responsive γδ T cells: novel effector cells in antibody-mediated kidney allograft microcirculation lesions.

Human cytomegalovirus infection in transplant recipients has been associated with adverse renal allograft outcome and with a large γδ T-cell response, but whether both mechanisms are connected is unknown. We previously showed that most expanded circulating cytomegalovirus-responsive γδ T cells express the Fcγ-receptor CD16, suggesting that γδ T cells may participate in allograft lesions mediated by donor-specific antibodies through antibody-dependent cellular cytotoxicity. Here, we show that cytomegalovirus-specific CD16(pos) γδ T cells can perform antibody-dependent cellular cytotoxicity against stromal cells coated with donor-specific antibodies in vitro. In vivo, graft-infiltrating γδ T cells localized in close contact with endothelial cells only in patients who experienced cytomegalovirus infection and were more frequent within peritubular capillaries and glomeruli from antibody-mediated acute rejections than within those from T cell-mediated acute rejections. Finally, a persistently increased percentage of circulating cytomegalovirus-induced γδ T cells correlated inversely with the 1-year eGFR only in kidney recipients with donor-specific antibodies. Collectively, these data support the conclusion that cytomegalovirus-induced γδ T cells are involved in, and may serve as a clinical biomarker of, antibody-mediated lesions of kidney transplants. Moreover, these findings offer a new physiopathologic link between cytomegalovirus infection and allograft dysfunction in recipients with donor-specific antibodies.

Safety of meglumine gadoterate (Gd-DOTA)-enhanced MRI compared to unenhanced MRI in patients with chronic kidney disease (RESCUE study).

OBJECTIVE: To prospectively compare the renal safety of meglumine gadoterate (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) to a control group (unenhanced MRI) in high-risk patients. METHODS: Patients with chronic kidney disease (CKD) scheduled for MRI procedures were screened. The primary endpoint was the percentage of patients with an elevation of serum creatinine levels, measured 72 ± 24 h after the MRI procedure, by at least 25 % or 44.2 µmol/l (0.5 mg/dl) from baseline. A non-inferiority margin of the between-group difference was set at -15 % for statistical analysis of the primary endpoint. Main secondary endpoints were the variation in serum creatinine and eGFR values between baseline and 72 ± 24 h after MRI and the percentage of patients with a decrease in eGFR of at least 25 % from baseline. Patients were screened for signs of nephrogenic systemic fibrosis (NSF) at 3-month follow-up. RESULTS: Among the 114 evaluable patients, one (1.4 %) in the Gd-DOTA-MRI group and none in the control group met the criteria of the primary endpoint [Δ = -1.4 %, 95%CI = (-7.9 %; 6.7 %)]. Non-inferiority was therefore demonstrated (P = 0.001). No clinically significant differences were observed between groups for the secondary endpoints. No serious safety events (including NSF) were noted. CONCLUSION: Meglumine gadoterate did not affect renal function and was a safe contrast agent in patients with CKD. KEY POINTS: • Contrast-induced nephropathy (CIN) is a potential problem following gadolinium administration for MRI. • Meglumine gadoterate (Gd-DOTA) appears safe, even in patients with chronic kidney disease. • Gd-DOTA only caused a temporary creatinine level increase in 1/70 such patients. • No case or sign of NSF was detected at 3-month follow-up.

Prediction of steroid-sparing agent use in childhood idiopathic nephrotic syndrome.

BACKGROUND: About half of children with steroid-sensitive idiopathic nephrotic syndrome (INS) will develop steroid dependency or a frequently relapsing course requiring steroid-sparing agents (SSA). Because of the adverse effects of prolonged steroid treatment, the early identification of children at high risk of requiring SSA may be a useful diagnostic tool to tailor the therapeutic strategy. The aim of this study was to identify predictors of the need for SSA and derive a predictive model. METHODS: This was a retrospective hospital-based cohort study which included all children with steroid-responsive INS followed for at least 4.5 months. Cox regression modeling and decision curve analysis were performed. RESULTS: A total of 120 children (81 boys) with INS were included and followed up for a median time of 6.7 (range 0.4-24.1) years. Median age at diagnosis was 3.4 years. Seventy-two (60 %) children required a SSA after a median time of 10 months following initial diagnosis. Male children, age at disease onset, methylprednisolone pulse use, and time to achieve first remission were significantly associated with the outcome. Time to achieve remission only remained significant after adjustment: hazard ratio (HR) =1.9 [95 % confidence interval (CI) 1.5-2.5] if considered as a continuous variable, and HR=4.1 (95 % CI 1.9-8.6) when dichotomized using the 9-day threshold. The area under the receiver operating curve of the related predictive model was 0.81 (95 % CI 0.74-0.89), and the decision curve analysis demonstrated that this model performed better than any other strategy. CONCLUSIONS: Time to first remission is a strong predictor of the need for SSA in pediatric INS. Further prospective and impact studies are warranted to confirm the accuracy and benefit of our prediction model.