Kidney360最新文献

Abstract: The landscape of cancer survival has been positively affected by the introduction and dissemination of immunotherapy with the wide usage of immune checkpoint inhibitors (ICIs) and chimeric antigen receptors cell therapies (CAR-T). The success of these novel therapies can however be limited to a certain extent by systemic inflammatory toxicities affecting directly or indirectly the kidney. In the case of ICIs severe acute interstitial nephritis is the main adverse event and can lead to permanent discontinuation of the therapy. In turn, CAR-T cell therapy can cause cytokine release syndrome (CRS) and immune effector cell-associated hemophagocytic lympho-histiocytosis (IEC-HLH), with kidney damage through various mechanisms and be life-threatening. Prompt diagnosis and management of these entities is essential to preserve kidney function and ensure the best possible kidney and overall outcomes to cancer patients.

Abstract: Accurate assessment of glomerular filtration rate (GFR) is key in patients with cancer, to guide drug eligibility, adjust dosing of systemic therapy, and minimize the risks of undertreatment and systemic toxicity. Several aspects of GFR evaluation in patients with cancer have been unclear, such as the choice of the GFR estimating equation and the overall lack of data on the reliability of new filtration markers, such as cystatin C. This uncertainty has led to concerns that inaccurate GFR estimation may have a large impact on clinical practice and research. Recent data have brought important developments to the field. The new and timely KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease raised important considerations and provided guidance on key aspects of GFR evaluation in patients with cancer. The guidelines cover valid estimating equations, incorporation of cystatin C in GFR estimation, drawbacks of using race, and acknowledge that non-GFR determinants of filtration markers may be prominent in certain patients, reducing the accuracy of GFR estimating equations, prompting greater utilization of GFR measurement. The aim of this review is to summarize advances in GFR evaluation in patients with cancer, considering the new KDIGO guidelines and other recent data.

Background: This study investigated risk factors and possible mechanisms of arterial and venous thromboembolic events in patients with pMN.

Methods: Patients with pMN confirmed by renal biopsy from June 1, 2010 to March 3, 2023 were included, and the study outcome was set as a composite endpoint of acute coronary syndrome, heart failure, cerebral infarction, arrhythmia, pulmonary embolism, deep venous thrombosis and all-cause mortality.

Results: A total of 433 pMN patients with complete data were included, with a median follow-up time of 73 (45.5-101.6) months and a composite endpoint rate of 10.2%. We divided all patients with events into early event group (events occurring in the first 2 years after renal biopsy) and late event group (events occurring after 2 years after renal biopsy) according to the time of event. It showed a lower serum albumin and a higher baseline value of serum PLA2R antibody titer and mean value of each follow-up in the early event group compared with the late event group. Cox proportional hazards model showed that after adjusting for confounding factors, in addition to older age, history of deep vein thrombosis and higher urinary protein, higher baseline serum PLA2R antibody titers (OR 1.034, 95% CI 1.006 -1.063, P = 0.015), and high hsCRP level (OR 1.049, 95% CI 1.002 -1.098, P = 0.041), renal pathology with segmental sclerotic lesions (OR3.480, 95% CI 1.338 -9.050, P = 0.011) were also independent risk factors for the occurrence of endpoint events. The results also showed that baseline serum IL-6 levels were significantly higher in the event group compared with the non-event group (4.25 pg/ml vs. 3.21 pg/ml), and the difference was statistically significant (P = 0.009).

Conclusions: In the early event group, higher serum PLA2R antibody and renal pathology with segmental sclerosis lesions may affect the occurrence of cardiovascular and cerebrovascular events and venous thrombotic events. The inflammatory system may play a role in this relationship.

Background: Post-kidney transplant adenovirus nephritis is a condition with potential for acute allograft dysfunction, and evidence on its management is scarce.

Methods: The present study is an original case series based on kidney biopsy of seven patients obtained at a health center specialized in kidney pathology from 2009 to 2023. We also performed a non-systematic literature review on cases described in the literature.

Results: Kidney biopsy was used to define the diagnosis of all patients. The average time to diagnosis after transplantation was 32.9 months. The most prevalent symptoms were fever, macroscopic hematuria, and dysuria. The glomerular filtration rate (GFR) reduced on average four times in relation to the baseline GFR. The main findings of kidney biopsy were acute tubular necrosis (100%), necrotizing granulomatous interstitial nephritis (100%) and viral inclusions (100%). The therapies used were human immunoglobulins, antivirals, and reduction of immunosuppression. The clinical course was favorable in six of the seven patients. Our literature review found 44 cases of adenovirus interstitial nephritis, and the outcome was favorable in the majority of reported cases.

Conclusions: Adenovirus interstitial nephritis is a rare condition, but with important implications for kidney transplant recipients. Kidney biopsy plays a very important role in confirmation. This study fills gaps in the current literature on adenovirus interstitial nephritis and contributes to the understanding of this potential complication in the follow-up of kidney transplant recipients.

Background: Chronic Kidney Disease (CKD) is a significant public health issue globally. Its progressive nature calls for innovative care models to mitigate disease progression and enhance patient outcomes. An interdisciplinary clinic model may offer comprehensive care tailored to the needs of CKD patients. The aim of this study is to evaluate the impact of an interdisciplinary CKD clinic on disease progression, healthcare utilization, and social determinants of health (SDOH).

Methods: We conducted a retrospective cohort study at the Mayo Clinic in Rochester, Minnesota. The study included 534 patients enrolled in the CKD clinic between March 5, 2021, and May 31, 2022, excluding those who opted out of research. The intervention involved a clinical registry and an interdisciplinary team delivering evidence-based care pathways, patient education, shared decision-making, and care coordination. The primary outcomes assessed were CKD progression and healthcare utilization, while secondary outcomes examined the impact of social determinants of health (SDOH).

Results: At entry, the median age was 73 (IQR 64-79), with 60% at Stage IV or lower. Clinic Implementation correlated with a 26% decrease in hospital admissions (incidence rate ratio [IRR] 0.74, 95% confidence interval [CI] 0.60-0.91, p=0.004) and a 30% reduction in emergency visits (IRR 0.70, 95 % CI 0.57-0.87, p=0.001). Nephrology consultations increased by 46% (IRR 1.46, CI 1.34-1.60, p<0.001), reflecting enhanced specialized care. Lower exercise frequency and unemployment were linked to increased CKD progression and healthcare usage.

Conclusion: An interdisciplinary CKD clinic supported by a registry can potentially reduce healthcare utilization among CKD patients, with SDOH playing a critical role in disease management.

Background: Renal infarction is a rare medical condition, with most studies focusing on prevalence and risk factors. Very few studies examined long term outcomes, and to our knowledge there are no studies comparing patients with renal infarction to a control group for long term outcomes such as mortality or kidney replacement therapy (KRT). We used a hospital population database to examine incidence, prevalence and risk factors for renal infarction and long-term outcomes such as mortality and KRT, comparing patients with renal infarction to the general population and to a matched cohort.

Methods: Retrospective cohort study of adult patients from an Australian Local Health (2008- 2017). We examined the incidence and prevalence of renal infarction along with risk factors associated with a renal infarction. We compared patients with a renal infarction to the general population and a 1:5 matched cohort to examine risk of mortality and KRT. Logistic regression was used to examine risk factors for renal infraction with odds ratio (OR) and 95% confidence intervals (95%CI), and Cox proportional hazard regression was used to determine hazard ratio (HR).

Results: Of the 140,099 patients included a renal infarction occurred in 119 (0.1%) with a crude incidence of 1.9 per 10,000 patient years (95%CI 1.6- 2.2). Factors associated with the risk of a renal infarction were age (OR 1.17 by decade, 95%CI 1.06- 1.30), atrial fibrillation (OR 2.55, 95%CI 1.54- 4.28), valvular heart disease (OR 2.88, 95%CI 1.26- 6.57) and peripheral vascular disease (OR 7.69, 95%CI 4.54- 13.4). During follow-up there was no increased risk of mortality after adjusting for age and comorbidities (HR 1.19, 95%CI 0.89- 1.61). However, the risk of KRT was significantly elevated even after adjusted for confounder (HR 8.4, 95%CI 3.6- 19.7). These results remained valid in the matched analysis.

Conclusions: Renal infarction is an uncommon event. The risk of mortality is not significantly increased when compared to the general population after adjusting for confounders. However, the risk of KRT remains significantly increased.

Background: Alport syndrome (AS) is an inherited disorder characterized by progressive renal disease, hearing deficits, and ocular abnormalities. This study investigates phenotypic variability among individuals with identical autosomal genetic mutations in COL4A3 and explores the potential influence of modifier genes. The study focuses on three families carrying the same COL4A3 mutation (c.2083G>A, p.Gly695Arg) but exhibiting differences in phenotype. The objective is to elucidate interfamilial and intrafamilial variations and identify potential genetic modifiers contributing to these differences.

Methods: Three families from a cohort at the University of Utah were studied. Clinical data, blood, urine, and tissue samples were collected with informed consent. Whole-exome sequencing (WES) was performed to identify genetic variants, using the SureSelect Human All Exon Target Enrichment System. Variant calling and annotation were conducted with GATK, VEP, and PEDDY. Disease-gene prioritization was achieved using the Variant Annotation, Analysis, and Search Tool (VAAST), pVAAST, and the Phenotype Driven Variant Ontological Re-ranking Tool (PHEVOR). Modifier genes were identified through co-segregation analysis and functional annotation using public databases.

Results: The study highlighted significant phenotypic variability within and between families with the same COL4A3 mutation. Individuals with single mutations often presented mild phenotypes, such as isolated hematuria, while compound heterozygotes and digenic cases exhibited severe manifestations, including proteinuria, hearing loss, and chronic kidney disease (CKD). Modifier genes such as GRIP1, CCND1, and CYP3A7 were identified and linked to phenotypic variability, suggesting their potential role in disease progression.

Conclusions: The findings underscore the role of genetic modifiers in influencing phenotypic variability in AS. Understanding these modifiers is crucial for personalized therapeutic strategies and genetic counseling. Future research should validate these candidate genes through functional studies and larger cohorts to enhance clinical care and improve prognostic predictions for patients with AS.

Background: Kidney function is not routinely assessed during pregnancy. Several studies have proposed antepartum kidney function, particularly 2nd trimester kidney function, as a potential predictor of adverse pregnancy outcomes. It has been previously established that patients with Systemic Lupus Erythematosus are at increased risk for adverse pregnancy outcomes. The association between 2nd trimester kidney function and adverse pregnancy outcomes has not been evaluated in diverse patient populations, particularly among patients with high obstetrical risk.

Methods: In this observational study of pregnant patients with lupus in North America and Europe from 1995-2017, we used 2nd trimester creatinine and the estimated glomerular filtration rate (eGFR) to model the log odds of preeclampsia, preterm birth, low birthweight, fetal loss, and a composite of those outcomes. We incorporated these measures into a regression setting using fractional polynomials, and we further examined discrete formulations of eGFR.

Results: Among 684 pregnancies in patients with lupus, the mean 2nd trimester creatinine was 0.63mg/dL ± SD 0.26 and the median value 0.60 (IQR 0.50-0.70). At least 1 in 3 patients in this combined cohort experienced an adverse outcome. Mixtures of U-shaped and linear relationships between continuous kidney function and the log odds of adverse pregnancy outcomes were observed. Stratifying the cohort by diagnosis of lupus nephritis (active or in remission) or without diagnosis of nephritis, we found differences in the relationship between kidney function and adverse outcomes.

Conclusions: We observed high rates of adverse pregnancy outcomes in our diverse patient population comprised of pregnant patients with lupus with and without lupus nephritis. We identified complex relationships between 2nd trimester kidney function and adverse pregnancy outcomes that differed by the outcome and diagnosis of lupus nephritis.

Background: We examined sex differences in cause-specific mortality among men and women receiving maintenance dialysis and examined potential effect modification by age and race.

Methods: We identified all adults aged ≥ 18 years initiating dialysis between 2000 and 2020 from the United States Renal Data System (n=2.16 million; 43.3% women). Cause-specific mortality (i.e., cardiovascular (CVD), withdrawal, infection, cancer) was defined from the Centers for Medicare and Medicaid Death Notification Form. All individuals were followed from dialysis start date until death date, transplant, 10-years, or end of follow-up (December 31, 2021), whichever occurred first. Multivariable Cox proportional hazards models assessed the association between sex and 10-year cause-specific mortality, adjusting for demographic, clinical, and socioeconomic factors overall and stratified by age and race.

Results: Overall, 832,259 men (67.9%) and 658,043 women (70.4%) died receiving maintenance dialysis with median survival times of 2.69 (IQR,1.17-5.19) and 2.72 (IQR, 1.16-5.21) years, respectively. CVD was the leading cause of death (38.6% women; 40.2% men), followed by withdrawal (11.1% women; 9.6% men) and infections (9.8% women; 8.6% men). Overall, women had a 9% (adjusted Hazard Ratio: 1.09 [95%CI 1.08-1.11]) and 15% (1.15 [1.14-1.17]) higher likelihood of infection, and withdrawal -related mortality compared with men, respectively. Conversely, women had a 7% (0.93 [0.92-0.94]) and 10% (0.90 [0.87-0.92]) lower likelihood of CVD and cancer-related mortality, respectively, compared with men. By age, younger women (vs. men) aged 18-44 years had higher likelihood of excess mortality across all specific causes (including a 40% increased risk of withdrawal compared to men of the same age), while older women (vs. men) aged >75 years had a lower likelihood. By race, non-Hispanic Black women (vs. men) had higher mortality across all specific causes, but for all other races, sex differences were similar to the overall population.

Conclusions: A sex-specific approach that incorporates intersectionality of both age and race in the management of complications among dialysis patients may be recommended to mitigate excess mortality risks.