Frontiers in nephrology最新文献

This Festschrift in honor of Dr. Jeffrey Hymes, a distinguished leader in nephrology and a pioneer in the field of dialysis care. Dr. Hymes' career has been marked by his unwavering commitment to improving patient outcomes through innovative approaches and data-driven insights. His contributions have not only advanced the practice of nephrology but have also had a profound impact on the lives of countless patients.

Cardiovascular diseases are a leading cause of mortality in Saudi Arabia, accounting for approximately 42% of deaths. The "triple whammy" phenomenon-which combines angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, diuretics, and non-steroidal anti-inflammatory drugs-increases the risk of acute kidney injury, particularly in hypertensive patients. This study, which was conducted in small-scale hospitals in Jeddah from 2017 to 2022, assessed the incidence of the triple whammy phenomenon and the awareness of healthcare professionals of this condition. Of 5,654 patient records, 1,899 met the inclusion criteria, with 2.7% experiencing the triple whammy. A survey of 56 healthcare professionals revealed 75% unawareness, with pharmacists and dentists being the most affected. Access to over-the-counter non-steroidal anti-inflammatory drugs and gaps in training likely drive the incidence and awareness deficits. This phenomenon can lead to acute kidney injury, with mortality rates as high as 50%-80% in critically ill patients, and imposes significant costs, representing 5% of hospital budgets and 1% of the overall health expenditure. Interventions including education, pharmacist roles, and non-steroidal anti-inflammatory drug regulation are proposed. Limitations include the small-scale focus and the low survey sample, necessitating national studies to accurately measure incidence and to improve patient safety.

A 67-year-old male patient with limited-stage diffuse large B-cell lymphoma was on an R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy regimen. His Eastern Cooperative Oncology Group (ECOG) Performance Scale score was zero, indicating functional independence for activities of daily living. The patient was admitted to the intensive care unit (ICU) with septic shock in the presence of febrile neutropenia progressing to acute kidney injury, hypoxemic respiratory failure, and systemic arterial hypotension, in addition to the already established hematological dysfunction with thrombocytopenia. During his 32-day ICU stay, he required invasive mechanical ventilation, renal replacement therapy (RRT) and vasopressor drugs, with a focus on control of the infection. The patient was discharged from the ICU with sarcopenia and a serum creatinine level of 2.3 mg/dL, indicating a clearance rate of 24 ml/min/1.73 m². Oxygen supplementation was needed. What impact did critical illness, more specifically renal dysfunction, have on the planning of onco-hematological treatment in this patient?

Glomerular diseases represent a significant global health challenge, complicated by the intricate management required for their treatment. We examine the treatment burden associated with the immunosuppressive therapies used to manage these conditions, focusing on the efficacy, side effects, and financial implications of commonly used medications such as glucocorticoids, mycophenolate mofetil (MMF), cyclophosphamide, calcineurin inhibitors and Rituximab. Immunosuppressive treatments, while effective in controlling disease activity, can result in a variety of adverse effects ranging from gastrointestinal symptoms and bone marrow suppression to increased infection risks, necessitating careful monitoring and dose adjustments to mitigate these risks. Hence, the need for a balanced approach in therapy management, incorporating regular monitoring and potential dose modifications to enhance patient outcomes while minimizing side effects. Additionally, these treatments have an economic impact, particularly in lower-income regions where access to medication and the cost of medication can limit patient outcomes. There have been certain advancements in treatment modalities, such as the use of enteric-coated formulations and tailored dosing schedules, which aim to improve drug tolerability and adherence. By addressing these critical aspects, we aim to shed light on the ongoing challenges and developments in the management of glomerular diseases, emphasizing the need for continued research and innovation in therapeutic strategies to reduce the overall treatment burden and improve the quality of life for affected individuals.

Background: Membranous nephropathy (MGN) represents a significant challenge in nephrology, with Rituximab emerging as a potential therapeutic intervention.

Methods: A comprehensive systematic review was conducted using PubMed, EMBASE, and Web of Science databases, focusing exclusively on randomized controlled trials (RCTs) from January 2002 to November 2024. Stringent eligibility criteria were applied, including studies with at least ten participants, with data extracted by two independent reviewers. The meta-analysis utilized fixed and random effects models to assess Rituximab's efficacy and safety across multiple outcome measures.

Results: The meta-analysis revealed nuanced findings across different follow-up periods. At 6 months, complete remission rates showed non-significant odds ratios ranging from 2.12 to 2.48. By 12 months, the pooled odds ratio was 0.8085 (95% CI: 0.2238-2.9213), with complete remission rates varying between 13.8% and 19.4%. Notably, at 24 months, the common effects model demonstrated a statistically significant odds ratio of 5.0792 (95% CI: 2.2609-11.4107, p < 0.0001). Proteinuria reduction showed consistent improvement, with a median difference of 4.3225. Adverse event analysis indicated a relatively low risk, with an odds ratio of 0.9706 (95% CI: 0.5781-1.6297).

Conclusion: Rituximab demonstrates potential efficacy in treating MGN, with promising long-term outcomes and a favorable adverse event profile.

Objectives: To understand the difference in adverse events (AEs), healthcare resource utilization (HCRU), and kidney failure rates in immunoglobulin A nephropathy (IgAN) patients who initiated systemic glucocorticoid (SGC) treatment compared with those who did not.

Methods: The overall cohort was selected from patients with IgAN (ICD-10 codes N02.8 and N04.1) identified in the TriNetX Dataworks database between January 2011 and May 2022. New initiators of dexamethasone, prednisone, prednisolone, or methylprednisolone (SGC cohort) were propensity score (PS) matched 1:1 with patients who did not receive SGC (non-SGC cohort) based on their characteristics at diagnosis. The index date was the date of SGC initiation; for the non-SGC cohort, a pseudo-index date was assigned using the same lag from diagnosis to index date as their PS-matched pairs. Patients with kidney failure before the index/pseudo-index date and their 1:1 PS-matched pairs were excluded.

Results: The final analysis was conducted in 802 patients (401 PS-matched pairs, mean age 41.2 years, 55% male). Median duration of follow-up was 3.5 and 3.1 years for the SGC and non-SGC cohorts, respectively. Compared with the non-SGC cohort, patients in the SGC cohort had greater frequency of several AEs, including severe infections, greater annualized HCRU and costs, and greater incidence of kidney failure.

Conclusions: This study found that SGC therapy may increase adverse reactions and HCRU in IgAN patients, while comparatively providing no beneficial effects on preserving kidney function.

Background: Podocytopathies are a varied set of renal diseases in which podocytes are unable to perform their typical filtration function within the glomerulus. This typically leads to edema, proteinuria, and hypoalbuminemia early in life. Among podocytopathies, focal segmental glomerulosclerosis (FSGS) is characterized by histology demonstrating segmental and focal sclerosis of the glomerular tuft. FSGS affects an estimated 1-20 per one million individuals and leads to significant morbidity and mortality related to renal failure. While FSGS can be attributed to many causes, such as drug reactions and infections, underlying pathogenic genetic variants play an increasingly well-recognized role in this disease.

Case: A 38-year-old 46,XX female patient of self-reported Cambodian ancestry was evaluated due to her history of atypical uterovaginal morphology. She had a history of hypertension and nephrotic range proteinuria that was diagnosed early in adulthood. A kidney biopsy at that time revealed FSGS. Following worsening renal function and subsequent end-stage renal disease (ESRD), she underwent a kidney transplant at 33 years of age. After kidney transplant, she presented with hematocolpos and was found to have distal vaginal atresia and an arcuate uterus. She underwent vaginoplasty and then had regular menses. She was noted to have persistently elevated follicle stimulating hormone levels, consistent with primary ovarian insufficiency, but with normal anti-Müllerian hormone levels. Assessment of her family history was suggestive of other individuals in her family with similar renal disease and uterine differences. Genetic analysis identified a WT1 variant (c.1338A>C; p. =) of uncertain significance that is also present in her similarly affected mother. To help clarify the potential impact of this variant, we completed a mini-gene assay to detect in vitro splicing changes in the presence of the WT1 variant sequence uncovered in this individual. This demonstrated resultant aberrant splicing that further supports the pathogenicity of the uncovered variant for this individual.

Conclusions: To our knowledge, this represents the first case of a podocytopathy with co-occurring uterovaginal anomalies due to exon skipping in WT1. The patient exhibited a severe course of chronic kidney dysfunction requiring a kidney transplant. Clinical RNA sequencing to clarify variants impacting splicing remains challenging due to tissue- specific gene expression for genes such as WT1, thus, research-based assays may be beneficial to understand the consequence of rare or previously uncharacterized variants.