BMC Nephrology最新文献

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) related to congenital mutations impeding control of the alternative pathway of complement. Following approval of the complement C5 inhibitor eculizumab by the European Medicines Agency and the US Food and Drug Administration, initial guidelines suggested lifelong therapy. Yet, growing evidence indicates that discontinuation of eculizumab, or its long-acting form ravulizumab, is possible for many patients. This mixed-methods study sought to explore international experts' perspectives and experiences related to treatment duration in adult patients with aHUS, while also estimating the financial and potential health consequences of early discontinuation.

Methods: Between January and December 2023, we conducted 10 qualitative interviews with experts in the treatment of aHUS, based upon which we constructed a quantitative decision tree, designed to estimate time on treatment and treatment- and disease-related adverse events.

Results: Thematic analysis of the interview data identified four main themes: (1) Concerns and prior experience; (2) High-risk vs. low-risk groups; (3) Patient preference and adherence; and (4) Funding for monitoring and re-treatment. Although most interviewees were in favour of considering treatment discontinuation for many patients (citing the high cost, burden, and potential side effects of lifelong treatment as key reasons), a prior negative experience of discontinuation seemed to make others more reluctant to stop. Deciding which patients required lifelong treatment and which not involved consideration of a wide range of factors, including patient- and system-related factors. Cost-consequence analysis demonstrated the financial savings associated with early treatment discontinuation at the expense of increased risk of recurrent TMA events. Close monitoring for these events had the potential to minimise any long-term injury, primarily renal, with an estimated one event per 100 patient years. For patients at high risk of TMA and with poor adherence to monitoring, rates of renal injury rose to three events per 100 patient years.

Conclusions: aHUS treatment protocols are changing globally in response to new clinical evidence. Against this backdrop, our mixed-methods study provides compelling evidence on the complexity of factors influencing treatment discontinuation decisions in aHUS, as well as the financial and health consequences of early discontinuation.

Background: Karyomegalic interstitial nephritis (KIN) is a rare renal diagnosis associated with both genetic and medication etiologies. The primary gene associated with KIN is the FAN1 gene which encodes a protein responsible for DNA interstrand repair. Common medication triggers of KIN are chemotherapeutic agents, especially those which disrupt DNA structure such as carboplatin. Despite overlap between these mechanisms, it has not clearly been established if medication usage requires an underlying genetic predisposition for triggering KIN or if medications alone are sufficient. This ambiguous pathogenesis can make it difficult to appropriately assess risk of KIN development when starting patients on one of the known KIN-inducing therapies. Additionally, brentuximab vedotin, an antibody-drug conjugate directed against CD30, has not been previously implicated in KIN development.

Case presentation: We present a 49-year-old woman previously diagnosed with metastatic Hodgkin's lymphoma who was treated with doxorubicin, bleomycin, vinblastine, and dacarbazine, then 3 cycles of ifosfamide, carboplatin, etoposide, all of which were discontinued due to side effects. Following an episode of acute kidney injury, the serum creatinine was 1.09 mg/dL. She then received 2 doses of brentuximab, the serum creatinine rose, and the drug was discontinued. Kidney biopsy done 2 months after brentuximab and 5 months following ifosfamide therapies showed karyomegalic interstitial nephritis. Genetic evaluation showed no FAN1 gene mutations. The patient was started on pembrolizumab; no steroids were given due to concerns about interference with lymphoma immunotherapy. She remains with stable disease and stable chronic kidney disease.

Conclusions: This case presents a patient who developed KIN with a progressively rising serum creatinine after ifosfamide, carboplatin and brentuximab treatment. Although ifosfamide and carboplatin have known associations with the development of KIN, this case raises the possibility that brentuximab, which has a different mechanism of action, also may be associated with KIN. Additionally, the genetic findings demonstrate that drug-induced KIN can develop in the absence of FAN1 mutations, a finding not previously reported.

Background: Chronic kidney disease (CKD) is a global health problem affected by under-recognition and under-treatment in primary care settings. Electronic clinical decision support (CDS) triggering systems have the potential to improve detection and management of people with CKD by assisting clinicians in adhering to guideline recommendations. We aimed to test whether an electronic CDS triggering system would improve the detection, recognition, and management of patients with CKD in primary care.

Method/design: This is a pragmatic cluster-randomized controlled trial where 66 primary healthcare centers from the Stockholm Region, Sweden were randomized 1:1 to receive either a new expanded CDS-triggering system offering kidney-specific advice or to continue with their current CDS-triggering system. The expanded CDS system reminds and provides practical facilitators of the processes of CKD screening, recognition with a diagnosis, management and referral to specialist care. The trial duration is 24 months and it is embedded into the Stockholm CREAtinine measurements (SCREAM) project, a repository of healthcare data from the region, which minimizes disturbances with healthcare praxis due to the trial and makes it fully pragmatic. The primary outcomes are the number of eligible patients screened for creatinine and albuminuria once annually and the re-testing of these labs within 6 months in patients with abnormal eGFR or albuminuria. Secondary outcomes are the proportions of issued clinical diagnoses among those fulfilling criteria, proportions of patients with significant albuminuria receiving prescribed nephroprotective medications, proportions of accepted referrals to nephrologist care among those fulfilling criteria and proportion of referrals for ultrasound of the kidneys.

Discussion: Prior pragmatic trials of CDS-systems in CKD has shown an improvement in quality indicators primarily in patients already diagnosed with CKD. This study expands this evidence by focusing on the process of screening, identification, monitoring and diagnostic work-up.

Conclusion: This pragmatic trial will assess the value of CDS for improved adherence to CKD guidelines in primary care.

Clinicaltrials: gov registration: NCT06386172, submitted 2024-04-23.

Background: Interstitial Pneumonitis (IP) is one of the pulmonary complications associated with mammalian Target of Rapamycin-Inhibitors (mTOR-Is). Sirolimus and everolimus belong to mTOR-Is. According to studies, IP is caused by both.

Case presentation: This is a case report in a kidney transplant recipient. We want to present a case of IP after 50 months of sirolimus consumption. Sirolimus was discontinued, and cyclosporine was started. Thirty-seven months later, everolimus was prescribed as an alternative to cyclosporine due to the recurrence of skin Squamous Cell Carcinoma (SCC). Fortunately, no respiratory manifestations were seen after more than 8 years of everolimus consumption.

Conclusions: In conclusion, in cases with sirolimus-induced IP, discontinuation of sirolimus and replacement with everolimus are recommended after resolving clinical symptoms and pulmonary lesions.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) has been a major cause of significant morbidity and mortality. Acute kidney injury (AKI) has been seen in COVID-19-infected subjects, and it has frequently resulted in an abnormal estimated glomerular filtration rate. Colchicine, an immunomodulatory drug, was used in several studies in the early stages of the pandemic. Colchicine has been shown to prevent the development of renal failure in patients with Familial Mediterranean Fever (FMF). It has also been reported to reduce fibrosis, which plays a role in chronic kidney disease. We, therefore, aimed to investigate whether using Colchicine, in addition to standard care, was associated with better renal function in patients with severe COVID-19 infection.

Methods: This retrospective cohort study comprised 118 out of 605 hospitalized COVID-19 subjects. Some of the subjects (n = 50) received oral Colchicine plus standard care, called the Col ( +) group. The others (n = 68) received only the standard care, called the Col (-) group. The estimated glomerular filtration rate (eGFR) and other laboratory findings, including lymphocytes, D-dimer, and CRP, were analyzed.

Results: The D-dimer and serum creatine levels were significantly reduced in both groups. The number of lymphocytes showed a significant increase in both groups at discharge. The level of C-reactive protein (CRP) was significantly higher in the Col ( +) group than in the Col (-) group at admission. The reduction of SCr was considerably higher in the Col ( +) group than in the Col (-) group. Similarly, the improvement of eGFR was higher in the Col ( +) group than in the Col (-) group at discharge and 6-12 mounts follow-up.

Conclusion: Our findings indicated the use of Colchicine plus standard care was associated with improved renal function in hospitalized patients with severe COVID-19 infection.

Background: For critically ill patients with acute kidney injury (AKI), there remains controversy regarding the predictive factors affecting the discontinuation of continuous renal replacement therapy (CRRT). This study aims to explore factors associated with successful CRRT discontinuation in AKI patients and to develop predictive models for successful discontinuation.

Methods: We conducted a retrospective study on adult patients with AKI who received CRRT, sourced from the Medical Information Mart for Intensive Care (MIMIC-IV) database. Successful discontinuation of CRRT was defined as no CRRT requirement within 72 h after stopping CRRT. Predictive factors for successful discontinuation of CRRT were analyzed. Additionally, we utilized machine learning algorithms to develop predictive models, including logistic regression (LR), decision tree (DT), random forest (RF), XGBoost, and K-nearest neighbor (KNN).

Results: A total of 599 patients were included, of whom 475 (79.3%) successfully discontinued CRRT. Urine output, non-renal SOFA score, bicarbonate, systolic blood pressure, and blood urea nitrogen were identified as risk factors for successful CRRT discontinuation. The KNN model exhibited the highest area under the receiver operating characteristic curve (AUC) (0.870), followed by LR (0.739), DT (0.691), RF (0.847), and XGBoost (0.830). When incorporating all available variables, the AUCs for the LR, DT, RF, XGBoost, and KNN models were 0.708, 0.674, 0.875, 0.866, and 0.816, respectively. Considering the performance of the models in both scenarios, the ensemble learning models (RF and XGBoost) were demonstrated superior performance.

Conclusions: Our results identified factors associated with successful discontinuation of CRRT in AKI patients. Additionally, we developed promising machine learning models which provided a reference for future research.

Background: Kinesiophobia, an irrational fear-avoidance behaviour, can significantly impact the quality of life and prognosis of peritoneal dialysis patients. This study aimed to assess the prevalence of kinesiophobia in patients undergoing peritoneal dialysis and to analyse its influencing factors.

Methods: A total of 291 patients who visited the outpatient and ward of peritoneal dialysis in 7 tertiary hospitals in Jiangsu Province from December 2023 to March 2024 were selected as research subjects via the convenience sampling method. A cross-sectional survey was conducted using a general data questionnaire, the Tampa Kinesiophobia-11 Scale, the Chinese Version of the Multidimensional Fatigue Symptom Scale, and the Simplified Coping Style Questionnaire.

Results: The score obtained using the Tampa Scale for kinesiophobia in patients with peritoneal dialysis was 22.44 ± 7.46, with a prevalence rate of 69.1%. Binary logistic regression analysis revealed that no complications, daily exercise before illness, and positive coping styles were protective factors (p < 0.05), whereas fatigue and negative coping styles were risk factors for kinesiophobia in patients receiving peritoneal dialysis (p < 0.05).

Conclusions: The prevalence of kinesiophobia in patients receiving peritoneal dialysis was high but at a mild level. Medical staff should combine influencing factors to identify high-risk groups as early as possible, formulate targeted interventions to reduce the occurrence of kinesiophobia and mitigate adverse effects on peritoneal dialysis patients.

Gitelman Syndrome (GS) is a rare autosomal-recessive tubular disorder characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, hyperreninemic hyperaldosteronism, and normotension. Management of GS during pregnancy is particularly challenging due to pregnancy-associated renal physiological changes and due to controversial safety profiles regarding teratogenicity of medications commonly used for GS management in non-pregnant patients. We report a case of a 20-year-old female patient diagnosed of GS who was treated with amiloride during pregnancy and lactation due to persistent hypokalemia resistant to oral supplementation therapy. Use of amiloride facilitated control of hypokalemia and hypomagnesemia in the mother without causing any noticeable side effects in the newborn.

Background: Sacituzumab govitecan is an antibody-drug conjugate that is FDA approved for refractory metastatic triple-negative breast cancer. It targets the human trophoblastic cell-surface antigen 2 (Trop-2) with SN-38, a topoisomerase I inhibitor, attached to the antibody [1]. SN-38 breaks DNA strands and induces tumor apoptosis [2]. Acute kidney injury (AKI) is one of its adverse effects mainly prerenal due to gastrointestinal toxicity, but it has not been reported to cause acute tubulointerstitial nephritis (ATIN).

Case presentation: This report describes a rare adverse effect of sacituzumab govitecan, the approach to diagnosing the etiology of the patient's AKI, and the mechanism by which sacituzumab govitecan causes ATIN. A woman with metastatic ER positive, PR positive, HER2 negative breast cancer who was initiated on sacituzumab govitecan presents with vomiting and diarrhea, and findings of nephrotic-range proteinuria, negative anti-PLA2R antibody, and severe AKI requiring hemodialysis. She underwent kidney biopsy and pathology showed ATIN characterized by patchy interstitial inflammation alongside tubular injury without glomerular and vascular involvement. With intermittent renal replacement therapy, furosemide challenge, and a course of prednisone, the patient's kidney function recovered.

Conclusions: Sacituzumab has a high affinity for Trop-2 protein which is also expressed within the collecting ducts, and to a lesser extent, the proximal tubule. Individuals, such as this patient, who express a homozygous genotype for UGT1A1*28 allele are at increased risk for AKI from sacituzumab govitecan due to decreased glucuronidation of SN-38.

Background: The quantification of mRNA expression in urinary sediments is a reliable biomarker for various diseases. However, few studies have investigated the clinical relevance of urinary mRNA levels in IgA nephropathy (IgAN). Thus, we investigated the expression of urinary mRNAs and their clinical significance in IgAN.

Methods: Overall, 200 patients with biopsy-proven IgAN, 48 disease controls, and 76 healthy controls were enrolled. We identified the differential expression of mRNAs in renal tissue between patients with IgAN and normal subjects using the Gene Expression Omnibus dataset and selected candidate mRNAs. mRNA expression in the urinary sediment was measured using quantitative real-time polymerase chain reaction. Associations between urinary mRNA levels and clinicopathological parameters were analyzed and the predictive value of mRNAs for disease progression was evaluated.

Results: The urinary expression of CCL2, CD14, DNMT1, FKBP5, Nephrin, and IL-6 was significantly upregulated in patients with IgAN compared with healthy controls. C3, FLOT1, and Podocin levels were significantly correlated with renal function, where C3, FLOT1, and TfR levels were significantly correlated with urinary protein excretion. During follow-up, 26 (13.0%) patients with IgAN experienced disease progression, defined as a greater than 50% reduction in the estimated glomerular filtration rate or progression to end-stage renal disease. Urinary mRNA levels of FLOT1 (HR 3.706, 95% CI 1.373-10.005, P = 0.010) were independently associated with an increased risk of disease progression.

Conclusions: Our results suggest that urinary sediment mRNAs are a useful biomarker in IgAN patients. Further studies with larger sample sizes and longer follow-up durations are required.