Representation of Low- and Middle-Income Countries in CKD Drug Trials: A Systematic Review.

RATIONALE & OBJECTIVE: Almost 80% of individuals with chronic kidney disease (CKD) reside in low- and middle-income countries (LMICs) and are potentially underrepresented in randomized controlled clinical trials (RCTs). We assessed the global distribution of RCTs comparing pharmacological treatments for CKD over the past 2 decades, as well as the magnitude and evolution of participation by LMICs. STUDY DESIGN: Systematic review. SETTING & STUDY POPULATIONS: RCTs evaluating pharmacological interventions in adults with CKD. SELECTION CRITERIA FOR STUDIES: RCTs published between 2003-2023 and indexed in MEDLINE. DATA EXTRACTION: Each trial was reviewed and extracted independently by 2 investigators with disagreements settled by consensus or a third reviewer. ANALYTICAL APPROACH: RCT participation of World Bank-defined income groups and geographic regions were described, and the representation indices (RI) according to RCT participants and estimated CKD prevalences were calculated. RCTs were also categorized as global, regional, or national in scope. RESULTS: Among 7,760 identified studies, we included 1,366 RCTs conducted in 84 countries with 301,158 participants. National, regional, and global RCTs represented 85.4%, 3.5%, and 11.1% of studies, respectively. LMICs were included in 34.7% of RCTs. No RCTs included participants from low-income countries, and lower-middle-income countries participated in 13.2%. Of participants from RCTs with available information, 25.4% (n=64,843 of 255,237) were from LMICs. According to the RI, 6 LMICs were overrepresented (>1.25), 7 were adequately represented (0.75-1.25), and 26 were underrepresented (<0.75). Most global CKD RCTs (80.2%) included LMICs; however, LMIC participants constituted only 32.9% of the global trial population. We observed a positive trend in LMIC inclusion over time, rising from 22.9% (n=71of 310) in 2003-2007 to 45.5% (n=140of 308) in 2018-2023. LIMITATIONS: The use of an income-group dichotomy, exclusion of nonrandomized studies of intervention, and studies identified in 1 database. CONCLUSIONS: Despite an increase in participation over the past 2 decades, individuals with CKD from LMICs remain significantly underrepresented in RCTs. These findings suggest that increased efforts are warranted to increase LMIC representation in pharmacological CKD RCTs. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) substantially affects people from low- and middle-income countries (LMICs). However, the participation of these countries in randomized controlled trials (RCTs) remains uncertain. To assess the global distribution and representation of these countries in kidney disease research, we reviewed 1,366 CKD drug RCTs published from 2003-2023, conducted in 84 countries involving more than 300,000 participants. LMICs were included in approximately a third of these studies, with their participants making up approximately one-quarter of the total; lower-middle-income countries were poorly represented, and low-income countries were absent. LMICs constituted a third of participants in multinational RCTs. Most LMICs were underrepresented relative to the prevalence of CKD. We observed an increasing inclusion of LMICs, particularly in the last decade. Nonetheless, individuals with CKD from LMICs remain underrepresented in drug RCTs, suggesting that increased efforts are warranted to include representation of these populations in these studies.

Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction.

INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

Diagnostic accuracy of the BioFire® FilmArray® pneumonia panel in COVID-19 patients with ventilator-associated pneumonia.

BACKGROUND: Ventilator-Associated pneumonia (VAP) is one of the leading causes of morbidity and mortality in critically ill COVID-19 patients in lower-and-middle-income settings, where timely access to emergency care and accurate diagnostic testing is not widely available. Therefore, rapid microbiological diagnosis is essential to improve effective therapy delivery to affected individuals, preventing adverse outcomes and reducing antimicrobial resistance. METHODS: We conducted a cross-sectional study of patients with suspected VAP and COVID-19, evaluating the diagnostic performance of the BioFire® FilmArray® Pneumonia Panel (FA-PP). Respiratory secretion samples underwent standard microbiological culture and FA-PP assays, and the results were compared. RESULTS: We included 252 samples. The traditional culture method detected 141 microorganisms, and FA-PP detected 277, resulting in a sensitivity of 95% and specificity of 60%, with a positive predictive value of 68% and negative predictive value of 93%. In samples with high levels of genetic material (> 10^5 copies/mL), the panel had a sensitivity of 94% and specificity of 86%. In addition, 40% of the culture-negative samples had positive FA-PP® results, of which 35% had > 10^5 copies/mL of genetic material. The most prevalent bacteria were Gram-negative bacilli, followed by Gram-positive cocci. The panel identified 98 genes associated with antimicrobial resistance, predominantly extended-spectrum beta-lactamases (28%). CONCLUSION: The FA-PP is a sensitive assay for identifying bacteria causing VAP in patients with COVID-19, with a greater capacity to detect bacteria than the conventional method. The timely microbiological recognition offered by this panel could lead to optimized decision-making processes, earlier tailored treatment initiation, and improved antibiotic stewardship practices.

Kidney growth progression patterns in autosomal dominant polycystic kidney disease.

BACKGROUND: Prognosis for autosomal dominant polycystic kidney disease (ADPKD), the main inherited cause of kidney failure, relies on estimating cystic growth using linear formulas derived from height-adjusted total kidney volume (Ht-TKV). However, nonlinear renal growth patterns may occur in typical ADPKD. AIMS: To determine kidney outcomes of subjects diagnosed with typical ADPKD exhibiting nonlinear, and unpredictable cystic growth during follow-up. METHODS: Retrospective cohort study. We categorized TKV changes in individuals with typical ADPKD according to observed kidney growth trajectories. Ht-TKV was calculated from consecutive CT or MRI using the ellipsoid method. We compared estimated glomerular filtration rate (eGFR) trajectories with linear mixed models. RESULTS: We included 83 individuals with ADPKD (67% women; age 47 ± 12 years; follow-up 5.2 years [IQR 2.8-9.0]). Three kidney growth patterns were observed: slow progression (24%, <3%/year linear increase), fast progression (39%, ≥3%/year linear increase), and atypical progression (37%, nonlinear growth). Adjusted ht-TKV change in mL/m/year was +1.4 (IQR -4.5 to +10.0), +40.3 (+16.9 to +89.3), and +32.8 (+15.9 to +85.9) for slow, fast, and atypical progressors, respectively (p < 0.001). Atypical progressors exhibited a significantly greater decline in eGFR in mL/min/m²/year (-7.9, 95% CI -6.5, -3.9) compared to slow (-0.5, 95% CI -3.1 to +0.5) and fast progressors (-3.4, 95% CI -7.9, -2.0; between-group p < 0.001). Atypical progressors had a higher proportion of acute complications, including hemorrhages, infections, and urolithiasis (84%), compared to slow (20%) and fast progressors (31%) (p < 0.001). CONCLUSION: In typical ADPKD, nonlinear, abrupt, and unpredictable cyst growth occurs frequently, leading to a higher risk of acute complications and kidney function decline.

Trephinations, Trephines, and Craniectomies: Contrast Between Global Ancient Civilizations and Pre-Hispanic Mexican Cultures.

Mesoamerica is culturally rich in diverse aspects, such as nature, sociology, and archeology. Several neurosurgical techniques were described during the Pre-Hispanic era. In Mexico, various cultures, such as the Aztec, Mixtec, Zapotec, Mayan, Tlatilcan, and Tarahumara, developed surgical procedures using different tools to perform cranial and probably brain interventions. Trepanations, trephines, and craniectomies are different concepts utilized to describe skull operations, which were conducted to treat traumatic, neurodegenerative, and neuropsychiatric diseases, and as a prominent form of ritual practice. More than 40 skulls have been rescued and studied in this region. In addition to written medical sources, archeological vestiges allow a more profound comprehension of Pre-Columbian brain surgery. The purpose of this study is to present the existing evidence of cranial surgery in Pre-Hispanic Mexican civilizations and their worldwide counterparts, procedures that have contributed to the global neurosurgical armamentarium, and have significantly impacted the medical practice's evolution.

Giant Cell Tumor of the Thoracic Spine in a Young Female Patient in a México City Spine Center: A Case Report.

BACKGROUND Giant cell tumors of the bone (GCTB) are rare, locally aggressive benign neoplasms that primarily occur in the metaphyses of long bones. In less than 2% of cases, GCTBs arise in the spine, predominantly below the sacrum. We report the clinical manifestations, diagnostic approach, and successful surgical treatment of a patient with a GCTB of the thoracic spine. CASE REPORT A 21-year-old female patient presented to the Emergency Department with back pain and upper motor neuron syndrome. A thorough clinical and imaging examination revealed a tumor and pathological fracture of the T7 vertebra. Histopathological analysis confirmed the diagnosis of a GCTB. The tumor was successfully excised surgically via a posterior thoracic approach, including bilateral decompressive laminectomy, lateral costotransversectomy, and posterior corpectomy, followed by transpedicular instrumentation of the T5-T6 and T8-T9 vertebrae, and anterior arthrodesis with an autologous graft. The patient also received adjuvant radiotherapy. One year later, the patient had no signs of recurrence or physical limitations. CONCLUSIONS GCTBs located in the thoracic spine are uncommon and pose a significant challenge for healthcare professionals due to their non-specific clinical manifestations and the need for a multidisciplinary approach to their management. This case highlights the diagnostic and therapeutic implications of a GCTB of the thoracic spine and describes a successful surgical strategy resulting in complete recovery. The presented case adds to the limited published literature on GCTBs in this unusual location and further elaborates on their presentation and management.

Optimizing peritoneal dialysis initiation: A comparative cohort study of catheter placement methods for shortening break-in periods.

INTRODUCTION: Peritoneal dialysis (PD) guidelines recommend a 14-day break-in period after catheter placement, yet this period could be shortened with new insertion techniques. METHODS: We conducted a prospective cohort study to compare percutaneous vs. surgical catheter insertion in a newly established PD program. The break-in period was intentionally shortened to <24 h to start PD almost immediately. RESULTS: We included 223 subjects who underwent percutaneous (34%) or surgical (66%) catheter placement. Compared to the surgical group, the percutaneous group had a higher proportion of early dialysis initiation within 24 h (97% vs. 8%, p < 0.001), similar successful initiation rates (87% vs. 92%, p = 0.34), and shorter lengths of stay (12 [9-18] vs. 18 [14-22] days, p < 0.001). Percutaneous insertion increased the likelihood of successful PD initiation within 24 h (OR 74, 95% CI 31-182), without increasing major complications. CONCLUSION: Percutaneous placement could represent a cost-effective and efficient technique to shorten break-in periods.

Long-term effects of hypercalcemia in kidney transplant recipients with persistent hyperparathyroidism.

BACKGROUND: Hypercalcemia is highly prevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain. METHODS: We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2 mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30 pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed. RESULTS: We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-up time, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64] mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40] pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4 ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300 pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80). CONCLUSIONS: Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipients in our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.

A Nonseminomatous Germ Cell Tumor Presenting as a Mixed Cryoglobulinemic Vasculitis.

Background: Mixed cryoglobulinemia syndrome (MCS) is a rare entity with a variety of causes but has not been associated with testicular germ cell tumors. We present here a case of a patient with a nonseminomatous germ cell tumor (NSGCT) presenting as a type III mixed cryoglobulinemic vasculitis. Case Presentation. A 58-year-old male exhibited typical clinical features of vasculitis, including weakness, fatigue, palpable purpura, multiple mononeuropathy, and a low C4 level. An MCS diagnosis was confirmed by the presence of cryoglobulins (6%) with polyclonal IgM and IgG components and biopsy proven leukocytoclastic vasculitis. Concomitantly, a stage IIIC (TxNxM1bS1) germ tumor with marked elevation of serum beta-human chorionic gonadotropin (2764 mUI/mL) was diagnosed. An aggressive treatment was needed, including methylprednisolone pulses, plasmapheresis, rituximab, followed by orchiectomy, and chemotherapy (bleomycin/etoposide/cisplatin). After tumor resection and treatment, cryoglobulins decrease to 0%, suggesting a paraneoplastic origin of the vasculitis. Conclusion: To the best of our knowledge, this is the first case of MCS possibly attributable to a NSGCT. This case further elaborates on the presentation of mixed cryoglobulinemia vasculitis and adds to the published literature on the topic.

Diagnostic performance of the Qiaprep amp Viral RNA UM kit for the detection of COVID-19 compared to RT-PCR.

Background: RT-PCR is the currently recommended laboratory method for diagnosing acute SARS-CoV-2 infection. Nevertheless, to carry out this assay, numerous manual steps are necessary, but they are long lasting and error-prone. A new sample preparation solution was launched, the Qiaprep & amp Viral RNA UM kit, that combines a short, liquid-based sample preparation with one-step RT-PCR amplification and detection of SARS-CoV-2. Such alternative allows reducing the handling of samples and obtaining a result in a shorter period of time. The objective of the study was to compare the performance of the kit with RT-PCR. Methods: A prospective trial was carried out in the clinical microbiology laboratory of a tertiary care hospital. The pharyngeal and nasopharyngeal swabs included in the study were taken from patients who underwent medical consultation because compatible COVID-19 symptoms. Samples were processed simultaneously for the reference RT-PCR and by the QIA P&A kit. Results: 190 samples were included in the clinical trial. The reference RT-PCR method indicated that 125 (66%) samples, out of the 190, were positive. The QIA P&A kit showed 112 positive samples for SARS-CoV-2. The QIA P&A kit has a sensitivity of 86% to detect SARS-CoV-2 and a 100% specificity, the positive predictive value was of 96%, the negative predictive value 78%, and the obtained Kappa value was 0,76. QIA P&A kit showed a lower mean cycle threshold compared with the diagnostic standard, with a statistically significant difference (p < 0.05). Conclusion: The QIA P&A kit has an acceptable, yet not optimal performance for sample preparation and amplification of SARS-CoV-2 and further studying is required for it to be validated as a cost-effective, rapid diagnostic method for detecting infections.

Low sensitivity of the COVID-19 antigen test (PANBIO™ COVID-19 Ag rapid test) to detect asymptomatic infections in health personnel of the National Institute of Respiratory Diseases.

Background: COVID-19 requires an early diagnosis to optimize management and limit transmission. SARS-CoV-2 is able to spread effectively. Infected asymptomatic individuals have been found to be contagious. RT-qPCR is the currently recommended laboratory method for diagnosing acute infection. However, rapid antigen detection (RAD) tests are not only fast, but require less specialized training. The possibility of using RAD tests to identify asymptomatic patients is attractive, as it could effectively contribute to minimizing the hospital spread of SARS-CoV-2. The objective of the study was to determine the performance of RAD vs. RT-qPCR for the detection of asymptomatic cases in INER health personnel. Methods: In order to follow WHO guidelines, generalized tests, a test station for health care workers was implemented on demand. A rapid test was carried out and a second sample was taken to be processed by RT-qPCR. With the results of both tests we conducted a retrospective study. Sensitivity, specificity, positive predictive value, negative predictive value and negative likelihood ratios were calculated. Results: A total of 1640 RAD tests were performed in health care workers (mean age was 39, 69, 47% with a self-reported comorbidity). Participants provided 1,640 valid RAD/RT-qPCR test pairs with 2% testing positive via RT-qPCR. 12 RAD samples were positive for SARS-CoV-2. Overall sensitivity of the PANBIO ™ COVID-19 Ag Rapid Test test was 35.2%. Conclusions: RADs are not recommended for the detection of asymptomatic cases due to low performance.