Nephrology Dialysis Transplantation最新文献

Background and hypothesis: Primary hyperoxaluria (PH) is a rare disorder with significant morbidity and mortality if left untreated. Given the rarity, global inequities in diagnostics and treatment are expected. Recently introduced RNA interference therapeutics (RNAi) have dramatically changed the outcome for PH patients, potentially disproportionately affecting low-resource regions. Understanding these disparities is crucial for implementing measures, ensuring equitable healthcare access for PH patients worldwide. This study aims to evaluate the current global health situation for PH patients upon the introduction of targeted therapeutics.

Methods: An international cross-sectional questionnaire study was conducted among healthcare providers involved in PH care. Responses were gathered between March 2023 and April 2024 and distributed by email via various international nephrology networks. Meta-analysis (mixed random effects model with inverse-variance weighting) was used to analyze data and adjust for subgroup differences.

Results: We gathered 136 responses from 57 countries, representing all World Bank regions. Overall access to genetic analysis diagnostics was 82% (CI, 77-91%) and to urinary oxalate measurement 97% (93-100%). Significant differences (P < 0.05) between low- and high-income countries were found for most diagnostics including genetic testing, plasma oxalate, plasma and urinary glycolate. Conservative therapies (e.g. pyridoxine and alkalinizing agents) were highly available globally (98% and 95%), but significant differences in access to peritoneal dialysis, kidney- and liver transplantation were reported (P < 0.05). Access to RNA interference therapeutic lumasiran was limited to high- and middle-income countries, with 53% (40-66%) of all countries having access (78% high-income versus 56% middle-income). Even in high-income countries, RNAi was not always accessible.

Conclusions: We found global disparities in access to optimal management of PH patients, disproportionately affecting low-income countries, but even existing between high-income countries. These results may provide support for initiatives to improve the outcome of PH patients worldwide in an era of new targeted therapeutic treatments.

Background and hypothesis: A more pronounced short-term increase in single-kidney GFR (ΔskGFR) has been associated with better long-term kidney function in living kidney donors. Whether this also applies to non-donors is unknown. We evaluated if ΔskGFR is associated with long-term risk of eGFR decline in individuals undergoing unilateral nephrectomy.

Methods: This study included 1777 participants from the SCREAM cohort who underwent radical unilateral nephrectomy in Stockholm between 2006-2021. The ΔskGFR was calculated as the early (1-6 months) post-nephrectomy eGFR minus 50% of the pre-nephrectomy eGFR. Multivariable Cox regression was used to study the association between Δsk-GFR and the subsequent risk of progressive eGFR decline, defined as composite of an eGFR decline > 30% compared to the early (6 months) post-nephrectomy eGFR or kidney failure.

Results: Mean age at nephrectomy was 68 ± 11 years, 40% were female, 92% had kidney cancer, and median (IQR) pre-nephrectomy eGFR was 76 (61-89) mL/min/1.73m2. Median Δsk-GFR was 11 (7-20) mL/min/1.73m2. Pre-nephrectomy determinants of Δsk-GFR were age (inverse association) and pre-nephrectomy eGFR (positive association). During a median follow-up of 5 years (range 0.6-15 years), 178 participants developed progressive eGFR decline. Individuals with a Δsk-GFR above the median had a lower rate of progressive eGFR decline (adjusted HR: 0.58, 95% CI: 0.42-0.80), compared to those with a Δsk-GFR below the median, independent of baseline eGFR and age.

Conclusions: A stronger increase in single-kidney eGFR early after unilateral nephrectomy was associated with a lower long-term risk of progressive eGFR decline. Evaluation of Δsk-GFR could help identify patients at higher risk of progressive kidney function decline following unilateral nephrectomy.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is caused by heterozygous germline variants in the fumarate hydratase (FH) gene [1,2]. Inheritance follows an autosomal dominant pattern. Loss of FH confers a predisposition for various benign and malignant neoplasms, including cutaneous leiomyomas, uterine fibroids and FH-deficient renal cell carcinoma [3]. While benign, cutaneous and uterine manifestations have a relevant impact on quality of life and risk for complications [4]. The vast majority of FH-deficient RCC exhibit an aggressive behavior with invasive growth and potential for early metastatic spread [5]. Additionally, pathogenic germline FH variants have been associated with other neoplasms, such as adrenal gland [10] and Leydig cell tumors [28, 29]. The aggressive behavior of FH-deficient RCC challenges nephron-sparing resection strategies, as a wide margin is recommended. Even after early nephrectomy for surgical removal of FH-deficient renal cell carcinomas, there is a relevant risk for distant metastasis as well as the remaining predisposition for de novo primary renal tumors in the other kidney. Active screening is central to HLRCC care since no preventative HLRCC-specific treatment exists. VEGF/EGFR directed treatment regimes, such as Erlotinib/Bevacizumab demonstrate efficacy against HLRCC-associated RCC [6]. This emphasizes the importance of establishing the correct diagnosis in HLRCC early on to guide therapeutic decisions. Morphologic criteria as well as specific immunohistochemical (IHC) staining and molecular genetics allow the identification of FH-deficient RCC. Changes made in the recent 2022 WHO classification impact the diagnosis of HLRCC in multiple ways. This commentary aims to point out this impact and to raise awareness among pathologists as well as clinicians involved in the care of patients with HLRCC.

Background: Music-based interventions (MBIs) have shown promise in enhancing cognitive and behavioral functions in patients with mild cognitive impairment (MCI). This review aims to synthesize current knowledge on the clinical application of MBIs in MCI and explore their potential use in patients with chronic kidney disease (CKD).

Methods: A systematic search was conducted in PubMed, PsycInfo, Cochrane Library, and Scopus databases for studies published between January 2013 and October 2023. The search focused on MBIs applied to MCI and CKD patients. We collected data on study design, type of MBIs administered and main clinical outcomes.

Results: Sixteen studies were included in this review, ten of which were randomized control trials (RCTs). MBIs ranged from passive music listening (4 studies) to active participation in music-making (vocal or singing activities, play instruments and improvisation, music interventions associated with physical activity, musical stimulation). While no studies specifically focused on CKD patients, cognitive improvements were generally more significant with active interventions, whereas behavioral benefits were more associated with receptive approaches.

Conclusions: MBIs showed potential benefits in improving cognitive and depressive symptoms associated with MCI. Given the high prevalence of MCI in CKD patients, future studies should investigate the application of MBIs in this population.

Background: Drug-induced acute interstitial nephritis (DI-AIN) represents a common cause of acute kidney injury. Early withdrawal of the culprit drug and corticosteroid therapy remains the mainstay of treatment.This study aimed to develop and validate a predictive nomogram to assess the probability of recovery of kidney function at 6 months after treatment.

Methods: Multicenter, retrospective, observational study in 13 nephrology departments. Patients with biopsy proven DI-AIN treated with corticosteroids between 1996-2023 were included. Dataset was randomly divided into training (n=164) and validation sets (n=60). Least absolute shrinkage and selection operator regression was used to screen the main predictors of complete (creatinine increase <25% of the last value before DI-AIN) or no recovery of kidney function (serum creatinine ≥75% or need for dialysis).

Results: The study group comprised 224 patients with DI-AIN: 51 (31%) in the training group and 19 (32%) in the validation set, achieved complete recovery at 6 months. Conversely, 33 (20%) and 8 (13%) patients in each set showed no recovery at 6 months. Clinical characteristics were well balanced between training and validation sets. The selected variables were age (under/above 65 years), gender, degree of interstitial fibrosis and time to corticosteroids initiation (under/above 7 days). Based on multivariable logistic regression model, a nomogram was developed. The area under the curve (AUC) of the nomogram was 0.79 (95% confidence interval: 0.71-0.88) indicating a good discriminative power. Bootstrap self-sampling was performed 1000 times for validation of the model. Calibration plot revealed that the predicted outcomes aligned well with the observations. Decision curve analysis suggested that the model had clinical benefit.

Conclusions: We developed and validated a nomogram to predict kidney recovery at 6 months in DI-AIN patients treated with corticosteroids. This tool helps clinicians estimate prognosis and optimize corticosteroid therapy's intensity and duration for better treatment outcomes.

Background: We investigated the long-term effect of COVID-19 on eGFR trajectory and the association with progression to kidney failure in patients with CKD.

Methods: Patients living with non-dialysis dependent CKD from British Columbia, Canada infected with COVID-19 (cases) were matched 1:2 to non-COVID-19 infected controls on variables including pre-COVID-19 annual rate of eGFR decline. Patients were followed from 90 days from the date of COVID-19 diagnosis. The Cox proportional hazards model was used for the primary outcome of kidney failure defined as a composite of eGFR reaching <15 ml/min/1.73m2, initiation of maintenance dialysis, or kidney transplantation. A linear mixed regression model was used to calculate the annual rate of change in eGFR.

Results: The study included 802 patients, 268 cases and 534 controls. Median age was 70 years and 54% were male. Over ∼3 years of follow up, the risk of developing kidney failure did not differ significantly between cases and controls. The annual rate of eGFR decline was -2.05 ml/min/1.73m2 among cases versus -1.35 ml/min/1.73m2 among controls representing a rate difference of 0.71 ml/min/1.73m2 (p-value= 0.02).

Conclusion: In patients with non-dialysis dependent CKD who survived at least 90 days without requiring dialysis, COVID-19 was not associated with an increased long-term risk of kidney failure over three years, but was associated with a greater annual decline in eGFR. Future research with longer follow-up is required to examine if this difference persists and leads to increased risk for kidney failure.

Background: The treatment strategy for non-AL amyloidosis monoclonal gammopathy of renal significance (MGRS) remains unstandardized. Autologous hematopoietic stem cell transplantation (ASCT) has shown favorable results in a limited number of studies.

Methods: This single-center, retrospective case-control study included non-AL amyloidosis MGRS patients diagnosed between February 2012 and July 2024; these patients were divided into the ASCT group and non-ASCT group. Baseline characteristics, ASCT characteristics and complications, treatment responses, survival outcomes, and risk factors for progression-free survival (PFS) were analyzed.

Results: A total of 53 patients with non-AL amyloidosis MGRS were enrolled in this study, comprising 23 patients who received ASCT and 30 patients who did not receive ASCT. The baseline characteristics were comparable between the ASCT and non-ASCT groups, with exceptions of serum albumin and C3 levels. The median OS and renal survival were not reached in either group. The median PFS was significantly longer in the ASCT group compared to the non-ASCT group (58.4 vs 16.4 months, P=0.004). The ORR and deep response rates of the ASCT group were higher than those of the non-ASCT group, both in hematological and renal responses. In the ASCT group, 18 patients (78.3%) achieved a hematological VGPR or better, and 21 patients (91.3%) achieved a renal PR or better after transplantation. Moreover, the ASCT group exhibited higher long-term cumulative incidences of OS and renal survival. The toxicity of ASCT was manageable, and no transplantation-related deaths occurred. There was no statistically significant difference in the median PFS between MIDD and LCPT (P=0.539). High serum albumin level at diagnosis, and hematological response ≥VGPR after ASCT were protective factors of PFS.

Conclusions: This study confirmed that ASCT was an effective and safe treatment for patients with non-AL amyloidosis MGRS, thereby offering long-term hematological remission and survival benefits.