Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study.

Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.

Use of peritoneal dialysis for acute kidney injury during the COVID-19 pandemic in New York City: a multicenter observational study.

To demonstrate feasibility of acute peritoneal dialysis (PD) for acute kidney injury during the coronavirus disease 2019 (COVID-19) pandemic, we performed a multicenter, retrospective, observational study of 94 patients who received acute PD in New York City in the spring of 2020. Patient comorbidities, severity of disease, laboratory values, kidney replacement therapy, and patient outcomes were recorded. The mean age was 61 ± 11 years; 34% were women; 94% had confirmed COVID-19; 32% required mechanical ventilation on admission. Compared to the levels prior to initiation of kidney replacement therapy, the mean serum potassium level decreased from 5.1 ± 0.9 to 4.5 ± 0.7 mEq/L on PD day 3 and 4.2 ± 0.6 mEq/L on day 7 (P < 0.001 for both); mean serum bicarbonate increased from 20 ± 4 to 21 ± 4 mEq/L on PD day 3 (P = 0.002) and 24 ± 4 mEq/L on day 7 (P < 0.001). After a median follow-up of 30 days, 46% of patients died and 22% had renal recovery. Male sex and mechanical ventilation on admission were significant predictors of mortality. The rapid implementation of an acute PD program was feasible despite resource constraints and can be lifesaving during crises such as the COVID-19 pandemic.

CoNTe: A Core Network Temporal Blockchain for 5G.

Virtual Network Functions allow the effective separation between hardware and network functionality, a strong paradigm shift from previously tightly integrated monolithic, vendor, and technology dependent deployments. In this virtualized paradigm, all aspects of network operations can be made to deploy on demand, dynamically scale, as well as be shared and interworked in ways that mirror behaviors of general cloud computing. To date, although seeing rising demand, distributed ledger technology remains largely incompatible in such elastic deployments, by its nature as functioning as an immutable record store. This work focuses on the structural incompatibility of current blockchain designs and proposes a novel, temporal blockchain design built atop federated byzantine agreement, which has the ability to dynamically scale and be packaged as a Virtual Network Function (VNF) for the 5G Core.

Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.

BACKGROUND: No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis. METHODS: In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to -1·50. Participants were randomly assigned to receive 20 µg of teriparatide once daily plus oral weekly placebo or 35 mg of oral risedronate once weekly plus daily injections of placebo for 24 months. The primary outcome was new radiographic vertebral fractures. Secondary, gated outcomes included new and worsened radiographic vertebral fractures, clinical fractures (a composite of non-vertebral and symptomatic vertebral), and non-vertebral fractures. This study is registered with ClinicalTrials.gov (NCT01709110) and EudraCT (2012-000123-41). FINDINGS: We enrolled 680 patients in each group. At 24 months, new vertebral fractures occurred in 28 (5·4%) of 680 patients in the teriparatide group and 64 (12·0%) of 680 patients in the risedronate group (risk ratio 0·44, 95% CI 0·29-0·68; p<0·0001). Clinical fractures occurred in 30 (4·8%) of 680 patients in the teriparatide group compared with 61 (9·8%) of 680 in the risedronate group (hazard ratio 0·48, 95% CI 0·32-0·74; p=0·0009). Non-vertebral fragility fractures occurred in 25 (4·0%) patients in the teriparatide group and 38 (6·1%) in the risedronate group (hazard ratio 0·66; 95% CI 0·39-1·10; p=0·10). INTERPRETATION: Among post-menopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures is significantly lower in patients receiving teriparatide than in those receiving risedronate. FUNDING: Lilly.

Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial.

IMPORTANCE: Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. OBJECTIVE: To determine the efficacy and safety of abaloparatide, 80 µg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture. DESIGN, SETTING, AND PARTICIPANTS: The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll. INTERVENTIONS: Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 µg (n = 824); or open-label teriparatide, 20 µg (n = 818) for 18 months. MAIN OUTCOMES AND MEASURES: Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants. RESULTS: Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text]. CONCLUSIONS AND RELEVANCE: Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01343004.

Fracture risk and zoledronic acid therapy in men with osteoporosis.

BACKGROUND: Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1199 men with primary or hypogonadism-associated osteoporosis who were 50 to 85 years of age to receive an intravenous infusion of zoledronic acid (5 mg) or placebo at baseline and at 12 months. Participants received daily calcium and vitamin D supplementation. The primary end point was the proportion of participants with one or more new morphometric vertebral fractures over a period of 24 months. RESULTS: The rate of any new morphometric vertebral fracture was 1.6% in the zoledronic acid group and 4.9% in the placebo group over the 24-month period, representing a 67% risk reduction with zoledronic acid (relative risk, 0.33; 95% confidence interval, 0.16 to 0.70; P=0.002). As compared with men who received placebo, men who received zoledronic acid had fewer moderate-to-severe vertebral fractures (P=0.03) and less height loss (P=0.002). Fewer participants who received zoledronic acid had clinical vertebral or nonvertebral fractures, although this difference did not reach significance because of the small number of fractures. Bone mineral density was higher and bone-turnover markers were lower in the men who received zoledronic acid (P<0.05 for both comparisons). Results were similar in men with low serum levels of total testosterone. The zoledronic acid and placebo groups did not differ significantly with respect to the incidence of death (2.6% and 2.9%, respectively) or serious adverse events (25.3% and 25.2%). CONCLUSIONS: Zoledronic acid treatment was associated with a significantly reduced risk of vertebral fracture among men with osteoporosis. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00439647.).

Cache-Oblivious parallel SIMD Viterbi decoding for sequence search in HMMER.

BACKGROUND: HMMER is a commonly used bioinformatics tool based on Hidden Markov Models (HMMs) to analyze and process biological sequences. One of its main homology engines is based on the Viterbi decoding algorithm, which was already highly parallelized and optimized using Farrar's striped processing pattern with Intel SSE2 instruction set extension. RESULTS: A new SIMD vectorization of the Viterbi decoding algorithm is proposed, based on an SSE2 inter-task parallelization approach similar to the DNA alignment algorithm proposed by Rognes. Besides this alternative vectorization scheme, the proposed implementation also introduces a new partitioning of the Markov model that allows a significantly more efficient exploitation of the cache locality. Such optimization, together with an improved loading of the emission scores, allows the achievement of a constant processing throughput, regardless of the innermost-cache size and of the dimension of the considered model. CONCLUSIONS: The proposed optimized vectorization of the Viterbi decoding algorithm was extensively evaluated and compared with the HMMER3 decoder to process DNA and protein datasets, proving to be a rather competitive alternative implementation. Being always faster than the already highly optimized ViterbiFilter implementation of HMMER3, the proposed Cache-Oblivious Parallel SIMD Viterbi (COPS) implementation provides a constant throughput and offers a processing speedup as high as two times faster, depending on the model's size.

Association of back pain with hypovitaminosis D in postmenopausal women with low bone mass.

BACKGROUND: Back pain is a major public health problem due to its high frequency, to the resulting activity constraint, and the need for surgery in many cases. Back pain is more frequent in women than men, mainly in postmenopausal women. High prevalence of hypovitaminosis D has been detected in postmenopausal women, and it is associated with decreased bone mass, sarcopenia, vertebral fractures, and inflammation, which can be related to back pain. METHODS: The relation between back pain and hypovitaminosis D was evaluated in this study, as well the difference regarding the number of bedridden days, number of days away from work, and daily activities limitation between women with and without hypovitaminosis D. This study reviewed baseline data from an interventional phase III multicenter trial in low bone mass postmenopausal women. The study included demographic data, 25OHD determinations, Newitt/Cummings questionnaire on back pain, and vertebral fracture identified thought X-ray evaluation. RESULTS: The trial included 9354 participants, but only 9305 underwent all the evaluations. The age median was 67 (60 - 85 years old) and age at menopause was 49 (18 - 72 years). Hypovitaminosis D was found in 22.5% of the subjects, 15.3% of them had vertebral fractures, 67.5% with back pain, and 14.8% reduced their daily activities in the previous six months. Subjects with hypovitaminosis D, compared to those without hypovitaminosis D, reported more back pain (69.5 v 66.9%, p: 0.022), more cases of severe back pain (8.5% v 6.8%, p: 0,004), higher limitation in their daily activities (17.2 v 14.0%, p: 0.001), and more fractures (17.4 v 14.6%, p: 0,002); also, they had more trouble to perform daily activities addressed in the Newwit/Cummings questionnaire. CONCLUSION: Hypovitaminosis D was related to back pain, to its severity, and to difficulty in perform daily activities. TRIAL REGISTRATION: ClinicalTrial.gov: NCT00088010.

Randomized clinical trial to evaluate the effect on postprandial glycemia of Nutren Control®, a glycemia-targeted specialized supplement, compared to standardized breakfast in patients with type-2 diabetes: the CONTROL DIABETES study.

Introduction: Objective: to evaluate the effects of a new glycemia targeted specialized supplement (GTSS) compared to a standard breakfast on postprandial blood glucose (PPG). Methods: patients with type 2 diabetes (T2D) and suboptimal control (A1C between 6.5 and 8.5 %) in monotherapy with metformin were included to this prospective, randomized, crossover trial. The standardized breakfast was isoenergetic compared to the GTSS, differing on macronutrients distribution. Both interventions were used once a day in the morning, each replacing breakfast for 7 consecutive days (14 days of observation). Intermittent scanning continuous glucose monitoring system (isCGM) determined the difference between the interventions regarding the incremental area under the curve (iAUC) of the PPG (3 hours after intervention), as a primary endpoint; secondary endpoints were the difference between the interventions regarding the glycemic peak, postprandial glucose excursion (PPGE), mean blood glucose (MBG) and time in range (TIR). Results: thirty-one T2D patients with ages between 39 and 69 years-old were enrolled. GTSS group had significantly lower iAUC of the PPG compared to standardized breakfast (33.3 [15.0 to 54.0] vs 46.8 [27.3 to 75.1] mg/dL), while also presenting a significantly lower PPG excursion (26.4 ± 17.2 vs 44.8 ± 24.4 mg/dL). There was no difference between the intervention periods regarding MBG, TIR and hypoglycemic events. Conclusion: The new GTSS, as a meal replacement in the breakfast, produced a 25 % reduction in the iAUC of the PPG, as accessed by isCGM, in comparison with an isocaloric-standardized meal.

Introducción: Objetivo: evaluar los efectos de un suplemento especializado en el control de la glucosa (GTSS) frente a un desayuno estándar sobre la glucemia posprandial (PPG). Metodología: es un estudio cruzado, prospectivo, aleatorizado en el que se incluyeron a pacientes con diabetes tipo 2 (T2D) con control subóptimo de la glucemia (HbA1c entre 6,5 y 8,5 %) utilizando monoterapia con metformina. El desayuno estandarizado fue isocalórico en comparación con el GTSS y solamente la distribución calórica fue diferente. Ambas intervenciones se utilizaron una vez al día por la mañana, reemplazando cada una el desayuno durante 7 días consecutivos (14 días de observación). Se utilizó el sistema de monitoreo continuo de glucosa (isCGM) para determinar las diferencias entre las intervenciones con respecto al área bajo la curva (iAUC) de glucosa postprandial (PPG) (3 horas después de la intervención) como variable principal o primaria; las variables secundarias fueron la diferencia entre las intervenciones con respecto al pico glicémico, la excursión de glucosa posprandial (PPGE), la glucosa media en sangre (MBG) y el rango de tiempo (TIR). Resultado: se incluyeron treinta y un pacientes con T2D con edades entre 39 y 69 años. El grupo del GTSS tuvo un área bajo la curva (iAUC) significativamente más baja de la PPG en comparación con el grupo del desayuno estandarizado (33,3 [15,0 a 54,0] frente a 46,8 [27,3 a 75,1] mg/dL), mientras que también presentó una PPG significativamente más baja (26,4 + 17,2 vs. 44,8 + 24,4 mg/dL). No hubo diferencia entre los períodos de intervención con respecto a la MBG, el TIR y eventos hipoglucémicos. Conclusión: el nuevo GTSS, como sustituto del desayuno, produjo una reducción de la iAUC de la PPG del 25 %, según el isCGM, en comparación con un desayuno isocalórico normalizado.

Immune abnormalities in IgA nephropathy.

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and it is characterized by mesangial IgA deposition. Asymptomatic hematuria with various degrees of proteinuria is the most common clinical presentation and up to 20%-40% of patients develop end-stage kidney disease within 20 years after disease onset. The pathogenesis of IgAN involves four sequential processes known as the "four-hit hypothesis" which starts with the production of a galactose-deficient IgA1 (gd-IgA1), followed by the formation of anti-gd-IgA1 IgG or IgA1 autoantibodies and immune complexes that ultimately deposit in the glomerular mesangium, leading to inflammation and injury. Although several key questions about the production of gd-IgA1 and the formation of anti-gd-IgA1 antibodies remain unanswered, a growing body of evidence is shedding light on the innate and adaptive immune mechanisms involved in this complex pathogenic process. Herein, we will focus on these mechanisms that, along with genetic and environmental factors, are thought to play a key role in disease pathogenesis.

Immune responses to SARS-CoV-2 in dialysis and kidney transplantation.

Despite progressive improvements in the management of patients with coronavirus disease 2019 (COVID-19), individuals with end-stage kidney disease (ESKD) are still at high risk of infection-related complications. Although the risk of infection in these patients is comparable to that of the general population, their lower rate of response to vaccination is a matter of concern. When prevention strategies fail, infection is often severe. Comorbidities affecting patients on maintenance dialysis and kidney transplant recipients clearly account for the increased risk of severe COVID-19, while the role of uremia and chronic immunosuppression is less clear. Immune monitoring studies have identified differences in the innate and adaptive immune response against the virus that could contribute to the increased disease severity. In particular, individuals on dialysis show signs of T cell exhaustion that may impair antiviral response. Similar to kidney transplant recipients, antibody production in these patients occurs, but with delayed kinetics compared with the general population, leaving them more exposed to viral expansion during the early phases of infection. Overall, unique features of the immune response during COVID-19 in individuals with ESKD may occur with severe comorbidities affecting these individuals in explaining their poor outcomes.

The Gut and Kidney Crosstalk in Immunoglobulin A Nephropathy.

Immunoglobulin A nephropathy(IgAN) is the most common primary glomerulonephritis worldwide. The working model for the pathogenesis of IgAN involves a multistep process starting from the production of galactose-deficient and polymeric immunoglobulin A-1 (gd-IgA1) that enters systemic circulation from gut-associated lymphoid tissue (GALT). Galactose-deficient IgA are targeted by endogenous IgG, leading to the formation of circulating immune complexes that deposit in the mesangium and resulting in glomerular inflammation. Disease onset and relapses are often associated with gut infections, supporting the hypothesis that the gut plays an important pathogenic role. In the presence of microbial pathogens or food antigens, activated dendritic cells in the gut mucosa induce T cell dependent and independent B cell differentiation into IgA secreting plasma cells. In IgAN patients, this promotes the systemic release of mucosal gd-IgA1. Not all bacterial strains have the same capacity to elicit IgA production, and little is known about the antigen specificity of the pathogenic gd-IgA1. However, efficacy of treatments targeting gut inflammation support a pathogenic link between the bowel immune system and IgAN. Herein, we review the evidence supporting the role of gut inflammation in IgAN pathogenesis.

Efficient alignment of pyrosequencing reads for re-sequencing applications.

BACKGROUND: Over the past few years, new massively parallel DNA sequencing technologies have emerged. These platforms generate massive amounts of data per run, greatly reducing the cost of DNA sequencing. However, these techniques also raise important computational difficulties mostly due to the huge volume of data produced, but also because of some of their specific characteristics such as read length and sequencing errors. Among the most critical problems is that of efficiently and accurately mapping reads to a reference genome in the context of re-sequencing projects. RESULTS: We present an efficient method for the local alignment of pyrosequencing reads produced by the GS FLX (454) system against a reference sequence. Our approach explores the characteristics of the data in these re-sequencing applications and uses state of the art indexing techniques combined with a flexible seed-based approach, leading to a fast and accurate algorithm which needs very little user parameterization. An evaluation performed using real and simulated data shows that our proposed method outperforms a number of mainstream tools on the quantity and quality of successful alignments, as well as on the execution time. CONCLUSIONS: The proposed methodology was implemented in a software tool called TAPyR--Tool for the Alignment of Pyrosequencing Reads--which is publicly available from http://www.tapyr.net.

Urine Microscopy for Internal Medicine Residents: A Needs Assessment and Implementation of Virtual Teaching Sessions.

Background: Although urine microscopy is an important step in the initial evaluation of a patient with kidney disease, internal medicine residents have minimal exposure to this technique during their training. The goal of this study was to understand knowledge of and attitudes toward urine microscopy among internal medicine residents and to implement virtual urine microscopy teaching sessions. Methods: A voluntary, anonymous, online survey was sent to all of the categorical internal medicine residents (n=131) training at the Icahn School of Medicine at Mount Sinai (ISMMS). The survey included 13 questions to assess attitudes toward, experience with, and clinical interpretation of urine microscopy specimens. In response to the survey results, we implemented virtual urine microscopy teaching sessions using video conferencing software that incorporated real-time urine sediment analysis with nephrology fellows and attending nephrologists. Results: The survey response rate was 45% (59 of 131). Forty-seven percent (28 of 59) of respondents reported performing urine microscopy at least once during their training, and 75% (44 of 59) of respondents did not feel comfortable performing urine microscopy. The majority of residents (92%; 54 of 59) reported they felt urine microscopy was very helpful or somewhat helpful in the evaluation of patients with AKI. Overall, 41% of responses to clinical interpretation questions were considered correct. Following survey completion, virtual urine microscopy sessions were held monthly and well received by the participants. Conclusions: Our study found that internal medicine residents perceive urine microscopy as a helpful diagnostic tool, although lack the skills to perform and interpret urine microscopy sediments. Virtual educational sessions using video conferencing software are a technically feasible approach to teaching urine microscopy to internal medicine residents. Future studies include a study of the effect of these sessions on learning of urine microscopy. Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2021_01_28_KID0006282020.mp3.

COVID-19 and the Kidney: A Worrisome Scenario of Acute and Chronic Consequences.

Acute kidney injury (AKI) is a common finding in patients with coronavirus disease 2019 (COVID-19) and has been associated with higher rates of death when compared to COVID-19 patients without kidney injury. Whereas the definitive pathogenesis of COVID-19-related AKI (CoV-AKI) is not clear, histopathologic evidence seems to point at multiple etiologies for the disease, including indirect and direct viral kidney injury. The high incidence of CoV-AKI, along with the aggressive clinical presentation of this entity, have increased the demands for kidney replacement therapies, rapidly overwhelming the supplies of healthcare systems even in major tertiary care centers. As a result, nephrologists have come up with alternatives to maximize the efficiency of treatments and have developed non-conventional therapeutic alternatives such as the implementation of acute peritoneal dialysis for critically ill patients. The long-term implications of CoV-AKI are yet unknown, though early studies suggest that around one third of the patients who survive will remain dependent on kidney replacement therapy. Nephrologists and healthcare workers need to be familiar with the clinical presentation and therapeutic challenges of CoV-AKI in order to develop strategies to mitigate the burden of the disease for patients, and for services providing kidney replacement therapies.

Recurrence of IgA Nephropathy after Kidney Transplantation in Adults.

BACKGROUND AND OBJECTIVES: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 "The Post-Transplant Glomerular Disease" study centers in Europe, North America, and South America. RESULTS: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence. CONCLUSIONS: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.

Effects of short-term risedronate on bone resorption and patient satisfaction in postmenopausal osteoporosis patients.

This multicenter, open-label study evaluated the effects of short-term risedronate on bone resorption and patient satisfaction in postmenopausal women with osteoporosis in Brazil. Entry requirements included: osteoporosis of the spine/femoral neck diagnosed by a bone mineral density (BMD) T-scoreor=1 dose of study drug (intent-to-treat [ITT] population), and 390 completed treatment (81%). After 12 wk, CTX decreased in 94% of patients (from 0.419+/-0.234 to 0.158+/-0.171 microg/L, p<0.0001). Mean CTX reduction was 60.6%. Patient satisfaction was good/excellent in 91.7% of patients. A total of 156 adverse events (AEs) were reported by 113 (23.5%) patients in the ITT population. Digestive symptoms emerged or worsened in 7.1% and 3.5%, respectively. Five patients (1.0%) experienced serious AEs, not considered to be related to risedronate. In conclusion, risedronate significantly reduced serum CTX after 12-wk treatment. Almost all patients reported good/excellent satisfaction.

Efficacy and safety of evogliptin in the treatment of type 2 diabetes mellitus in a Brazilian population: a randomized bridging study.

BACKGROUND: Evogliptin (EVO) is a potent and selective dipeptidyl peptidase-4 inhibitor (DPP4i) developed for the treatment of type 2 diabetes mellitus (T2DM). DPP4is are known to exhibit a better glucose-lowering effect in Asians compared to other ethnic groups. Once EVO's clinical development program was conducted in Asian patients, this bridging study was designed to validate for the Brazilian population the efficacy and safety of the approved dose regimen (once-daily 5.0 mg). METHODS: In this randomized, double-blind, double-dummy, parallel trial, 146 patients with T2DM with inadequate glycemic control on diet and exercise (7.5% ≤ HbA1c ≤ 10.5%) were randomly assigned to a 12-week once-daily treatment with EVO 2.5 mg (N = 35), EVO 5 mg (N = 36), EVO 10 mg (N = 36), or sitagliptin (SITA) 100 mg (N = 39). Absolute changes (Week 12-baseline) in HbA1c, fasting plasma glucose (FPG) and body weight (BW) were obtained. One-sided one sample t test was used to determine if mean HbA1c reduction in each group was < - 0.5% (beneficial metabolic response). An analysis of covariance estimated the change in HbA1c and FPG adjusted by baseline HbA1c, FPG, body mass index (BMI) and study site. Response rates to treatment were also established. No between-group statistical comparisons were planned. RESULTS: HbA1c mean reductions were - 1.26% (90% CI - 1.7%, - 0.8%), - 1.12% (90% CI - 1.4%, - 0.8%), - 1.29% (90% CI - 1.6%, - 1.0%), and - 1.15% (90% CI - 1.5%, - 0.8%) in groups EVO 2.5 mg, EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. FPG levels showed a mean increase of 10.89 mg/dL in group EVO 2.5 mg, with significant mean reductions of - 18.94 mg/dL, - 21.17 mg/dL, and - 39.90 mg/dL in those treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. BW showed significant reductions of approximately 1 kg in patients treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg. Mean adjusted reductions of HbA1c and FPG levels confirmed the significant clinical benefit of all study treatments. The clinical benefit of EVO's "target" dose (5 mg) was confirmed. No safety concerns were identified. CONCLUSIONS: These results validate for the Brazilian population the approved dose regimen of EVO (once-daily 5 mg).Trial registration ClinicalTrials.gov Identifier: NCT02689362 (first posted on 02/23/2016).