Clinical Kidney Journal最新文献

Background and hypothesis: Mild cognitive impairment and dementia (CI) are common in patients with CKD. We aim to clarify whether and how CKD and CI coexistence increases adverse health outcomes.

Methods: This retrospective observational cohort study was conducted on CKD patients (stages 3-5) from the TriNetX platform. CKD patients with and without pre-existing CI were included from 115 healthcare organizations, and their outcomes were compared. The two cohorts were propensity score matched (PSM) for age, sex, ethnicity, comorbidities, BMI, blood parameters, and medications. The proportional hazard assumption was tested with a 95% confidence interval. Kaplan-Meier analysis was used to calculate survival probability. Outcomes were included from 1 day after the CKD diagnosis until 10 years afterwards.

Results: We identified 533 772 CKD patients, and 8184 had co-existent CI. Two cohorts of 8170 PSM patients each were generated. The mean age was 60.5 ± 7.0 years and the eGFR was 52.1±19 mL/min. Mean follow-up was 23.2 months. CKD patients with CI had higher all-cause mortality (18.5% vs 12.6%), higher risk of cerebrovascular disease (11.3% vs 6.9%), transient cerebral ischemic attacks (2.7% vs 1.6%), hypotension (16.5%-12.5%), malnutrition (6.7% vs 4.0%), pneumonia (10.7% vs 7.9%), urinary infections (13.2% vs 9.3%), encephalopathy (9.9% vs 5.0%), mood disorders (13.6% vs 9.7%), psychosis (9.8% vs 4.6%), and epilepsy (4.3% vs 1.5%). Higher use of antidepressants (26.3% vs 16.3%), anticonvulsants (19.5% vs 15.1%), antipsychotics (18.6% vs 9.1%), anticholinesterase (5.6% vs 0.1%), and benzodiazepines (30.6% vs 26.6%) was noted in those with CI. All these findings were statistically significant.

Conclusion: Despite the limitations of a retrospective study, real-world data demonstrate that concomitant CI is a decisive risk factor for higher mortality and increased adverse outcomes in patients with CKD. These results highlight the need for routine comprehensive cognitive assessments in patients at any stage of CKD.

Background: This study aims to investigate the spectrum and prognosis of membranous nephropathy (MN) in patients with Sjögren's syndrome (SS).

Methods: SS patients with biopsy-proven kidney involvement who were diagnosed at our center between April 2007 and February 2024 were retrospectively reviewed and analyzed.

Results: A total of 290 SS patients with kidney involvement were enrolled. The frequency of MN increased from 16.28% during the 2007-2010 period to 44.05% during the 2021-2024 period. After 2016, MN became the most common renal pathologic type, surpassing tubulointerstitial nephritis. PLA2R antibody or antigen was detected in 74 SS-MN patients, in whom 37 (50%) showed a negative result. Within the PLA2R-negative group, five out of 15 showed positivity for EXT1/EXT2 antigen and one out of eight for THSD7A antigen. Sixty-one SS patients with MN were followed up for >6 months, and 44 (72.13%) of them achieved renal complete remission (CR). Compared with PLA2R-negative patients, PLA2R-positive patients spent a longer time to achieve CR (1.46 ± 1.16 vs. 0.74 ± 0.47 years, P = .015) and had a higher rate of progression to the renal endpoint (8/32 vs. 1/29, P = .028). After adjusting for age, proteinuria, and eGFR, Cox regression analysis showed that PLA2R positivity remained a risk factor for CR [HR = 0.511, 95% CI (0.262 to 0.998), P = .049].

Conclusions: MN has become the predominant renal pathologic type in SS. PLA2R-positivity testing followed by EXT1/EXT2 and THSD7A testing is recommended for SS-MN patients. Although most patients can achieve renal CR, the prognosis is usually poor in PLA2R-positive SS-MN patients.

Background: Chronic kidney disease (CKD) is a significant risk factor for cerebrovascular disease. However, there is limited research on how successful living donor kidney transplantation (LDKT) affects cerebral blood flow (CBF). This study aims to comprehensively investigate how LDKT influences CBF across various brain levels and regions.

Methods: Data from 53 recipients between 2016 and 2020 were obtained from the VINTAGE study conducted at our hospital. CBF was measured by level and region using single-photon emission computed tomography (SPECT), according to the Talairach brain atlas. The primary endpoint was the mean difference in CBF before and 1-year post-LDKT. Subgroup analysis using traditional risk factors assessed the heterogeneity of the effect on CBF in the frontal lobe region.

Results: LDKT improved blood flow in the anterior cerebral artery and middle cerebral artery but had less impact on the posterior cerebral artery. The most consistent improvements were observed in the frontal lobe region {left frontal lobe: -0.12 [95% confidence interval (CI) -0.18 to -0.05], P < .001; right frontal lobe: -0.13 [95% CI -0.21 to -0.05], P = .001}. Subgroup analysis showed a consistent effect of LDKT on frontal lobe CBF improvement, with no qualitative interaction observed.

Conclusions: LDKT contributes to the normalization of CBF, with improvement in anterior circulation and frontal lobe blood flow. To clarify the clinical significance of KT's CBF-improving effect, future studies should investigate the relationship between specific cognitive impairments (e.g. short-term memory, visuospatial ability, executive function) and CBF in each perfusion region.

Background: Although post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplantation, there are few data on prevention, optimal screening, and treatment strategies.

Methods: The European Renal Association's DESCARTES working group distributed a web-based survey to European transplant centres to gather information on risk assessment, screening procedures, and management practices for preventing and treating PTDM in kidney transplant recipients.

Results: Answers were obtained from 121/241 transplant centres (50%) across 15 European countries. Screening practices for diabetes mellitus during the transplant work-up varied, with only 13% of centres using the recommended oral glucose tolerance test (OGTT) and 14% not screening at all. At transplantation, 19% of centres tailored the immunosuppressive regimen based on perceived PTDM risk, using strategies such as cyclosporin use or early steroid withdrawal. Fifty-two percent adopted strict glycaemic control with basal insulin in the first days post-transplant. Sixty-eight percent had defined screening protocols for early PTDM (45 days-6 months), primarily based on fasting glycaemia and/or HbA1c, while only a minority (7%) incorporated an OGTT. Changes in immunosuppression were considered by 41% in cases of early hyperglycaemia (<45 days) and by 58% in established PTDM (>45 days). Besides insulin therapy, dipeptidyl peptidase-4 (DPP4) inhibitors and metformin were most frequently used to manage early hyperglycaemia (<45 days) and PTDM (>45 days). The use of SGLT2 inhibitors and GLP-analogues increased >45 days post-transplantation.

Conclusion: This European survey underscores the significant variation in PTDM prevention, screening, and treatment practices, emphasizing the imperative for more explicit guidance in approaching this complication.

Introduction: The calcium load test (CLT) was developed by Pak et al. in 1974 to better discriminate hypercalciuria. Absorptive hypercalciuria (AH) is defined by an increase of the difference between urinary calcium/creatinine ratio (ΔUCa/Cr) of more than 0.5 mmol/mmol with a 4-hour CLT. In clinical practice and more recent studies, CLT is a 2-hour test. We hypothesized that the 4 h timepoint is more efficient in AH diagnosis.

Methods: We report a single-centre retrospective study including all patients who underwent CLT because of hypercalciuria or hyperparathyroidism. After a 3-day low-calcium diet and a 12-hour fast, 24-hour urines were collected. Blood and urinary samples were done at arrival and after 2 h and 4 h of oral ingestion of 1 g of calcium. AH was diagnosed by ΔUCa/Cr between baseline and 2 h or 4 h of more than 0.05 mmol/mmol.

Results: We included 328 patients. Baseline UCa/Cr ratio was 0.3 ± 0.2 mmol/mmol and increased significantly after 2 h and 4 h (0.6 ± 0.3 and 0.8 ± 0.4 mmol/mmol, P < 0.001). ΔUCa/Cr was significantly different between baseline and 2 h or 4 h (0.2 ± 0.2 versus 0.5 ± 0.4, P < 0.001). AH was diagnosed in 35 (10.7%) patients after 2 h, 84 (25.6%) more were diagnosed at 4 h (P < 0.001).

Conclusions: The 4 h CLT improves the diagnosis of AH with more than 50% of AH diagnosed within 4 h of calcium ingestion. It seems that there are cases of AH of later diagnosis with a similar clinical and biological profile depending on enteral absorption.

Pre-emptive kidney transplantation (PKT) has long been considered the optimal treatment for patients with end-stage chronic kidney disease (CKD) seeking the most favourable long-term outcomes. However, the significant growth in transplant procedures over recent decades has led to a notable increase in wait-listed patients and a disproportionate demand for donor organs. This situation necessitates a re-evaluation of transplantation timing and the establishment of rational indications from both societal and clinical perspectives. An increasing number of retrospective analyses have challenged the universal benefit of PKT, suggesting that premature indications for living or deceased donor PKT may not always yield superior hard outcomes compared with non-PKT approaches. Conventional predictive models have shown limitations in accurately assessing risks for certain subpopulations, potentially leading to significant disparities among wait-listed patients. To address these challenges, we propose the following considerations. Prediction models should not only optimize the distribution of our limited donor resources, but should also illuminate foreseeable risks associated with a potentially 'unsuccessful' PKT. Therefore, this article seeks to underscore the necessity for further discourse on the smouldering concept of when and for whom living or deceased donor PKT should be considered. Is it universally beneficial, or should the clinical paradigm be re-evaluated? In the endeavour to attain superior post-PKT survival outcomes compared with non-PKT or conservative treatment, it seems critical to acknowledge that other treatments may provide more favourable results for certain individuals. This introduces the intricate task of effectively navigating the complexities associated with 'too early' or 'unsuccessful' PKT.

Background and hypothesis: The two apolipoprotein L1 (APOL1) variants, G1 and G2, are common in populations of sub-Saharan African ancestry. Individuals with two of these alleles (G1 or G2) have an increased risk for a spectrum of non-diabetic chronic kidney diseases. However, these variants are typically not observed outside of populations that self-identify as current continental Africans or having clear recent African ancestry such as, most notably, African Americans, and other large population groups in the Americas and several European countries. We hypothesized that the diverse ethnic groups within the Israeli population may exhibit varying levels of recent African ancestry. Therefore, it is plausible that APOL1 risk alleles might be present even in individuals who do not self-identify as being of sub-Saharan African descent.

Methods: We non-selectively screened people with kidney failure across Israel for APOL1 risk variants using restriction fragment length polymorphism.

Results: We recruited 1744 individuals from 38 dialysis units in Israel. We identified eight patients of Moroccan Jewish, Bedouin, or Muslim Arab ancestry, who carry at least one G1 or G2 allele. None of the eight patients carried the protective APOL1 p.N264K variant. Furthermore, despite all Bedouin individuals being G2 heterozygous, the G2 minor allele frequency was significantly enriched in kidney failure cases compared to ethnically matched controls (P = .006).

Conclusions: These findings show that APOL1 G1 and G2 allelic variants are present in populations previously not appreciated to possess recent sub-Saharan ancestry and suggest that a single G2 risk variant may confer increased risk for chronic kidney disease in certain population contexts.

Background: Sparsentan, a dual-acting antagonist for both the angiotensin II receptor type 1 and the endothelin receptor type A, has emerged as a promising therapeutic agent for the treatment of IgA nephropathy (IgAN). Following the publication of the PROTECT trial, sparsentan recently received approval for the treatment of IgAN in Europe. However, it remains uncertain whether an additive effect can be observed in the context of existing treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors, given that the PROTECT study did not investigate this dual therapy approach.

Methods: A total of 23 patients with IgAN were treated with sparsentan via the Managed Access Programme between December 2023 and August 2024. The patients were stable on maximum tolerated doses of renin-angiotensin system (RAS) and SGLT2 inhibitors, with an estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m² and a urine protein/creatinine ratio (UPCR) >0.75 g/g.

Results: In the 23 patients, median (IQR) baseline eGFR (CKD-EPI) was 42 mL/min/1.73 m² (32-63) and median baseline UPCR was 1.5 g/g (0.9-1.8). After initiation of sparsentan, UPCR significantly decreased (P < 0.0001) to a median of 0.85 g/g (0.42-1.15) in the 2-week follow-up and further declined (P = 0.001) to a median of 0.60 g/g (0.32-0.82) after 14 weeks, equivalent to a relative reduction in proteinuria up to 62% (45-74). A similar significant reduction was observed for the urine albumin/creatinine ratio. No drug-related serious adverse events were reported.

Conclusions: In this real-world setting, sparsentan shows a significant impact on proteinuria, leading to a relative reduction of 62% in UPCR after 14 weeks and beyond, even in patients already receiving SGLT2 inhibitors.

Introduction: The activation of the complement system plays an important role in the pathogenesis of IgA nephropathy (IgAN). Our primary aim was to evaluate a range of complement-related proteins, including pentraxin-3 (PTX-3), in blood and urine at diagnosis and their association with disease activity in the kidney biopsy, eGFR, albuminuria, and outcome. Our secondary aim was to compare the same biomarkers between patients with IgAN and IgA vasculitis with renal involvement (IgAVN).

Methods: In a longitudinal Swedish cohort of 96 patients with IgAN (n = 65) or IgAVN (n = 31), with a median follow-up time of 10.8 years, we analysed mainly lectin-pathway-related proteins and PTX-3 in plasma and urine (u) samples stored at the time of kidney biopsy. Outcome was defined by the GFR slope or by the combined outcome of 50% loss of eGFR or end-stage kidney disease (ESKD).

Results: Patients with detectable vs undetectable u-PTX-3 and u-mannose-binding lectin (MBL) more frequently had mesangial hypercellularity, endocapillary proliferation, and crescents in their kidney biopsy. u-C4c levels were higher in patients with advanced tubulointerstitial fibrosis, and u-C4c was also an independent predictor of a more severe eGFR slope. There were no differences in the levels of biomarkers between patients with IgAN and IgAVN.

Conclusion: u-PTX-3 and u-MBL might be biomarkers of an active proliferative stage of the disease, while higher u-C4c levels indicate more chronic lesions in both IgAN and IgAVN. These results must, however, be confirmed in larger and multiethnic cohorts.

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are recommended for reducing the renal and cardiovascular risk in patients with chronic kidney disease (CKD) based on the positive results reported by clinical trials. However, real-world data on the efficacy and the safety of these drugs in CKD population followed in nephrology setting are lacking.

Methods: We report the effects of dapagliflozin in CKD patients by using data collected during a learning program in which 105 nephrologists added dapagliflozin (10 mg/day) to consecutive patients referred to their renal clinics. Efficacy endpoints were the albuminuria change and the determinants of an albuminuria decline ≥30%. Adverse events were also collected.

Results: A total of 1724 patients with CKD (age 67.4 ± 13.2 years, 72.8% males, diabetes 59.9%, eGFR 43.5 ± 17.4 ml/min/1.73 m², severe albuminuria 70.1%) received dapagliflozin for 4 ± 1 months. Dapagliflozin significantly reduced body weight (-1.3 kg), eGFR (-0.27 ml/min/month), and blood pressure (-3.6/-1.7 mmHg). Albuminuria declined by 25.1% (95%CI 23.0-27.2) from 500 mg/day [IQR 225-1425] to 320 mg/day [IQR 100-900]. Albuminuria reduction was ≥30% in 48.3% of patients, 0-29% in 37.6% while it increased in 14.1% of patients. At logistic regression analysis, older age, female sex, use of mineralocorticoid receptor antagonist, higher eGFR, and higher albuminuria were all significant predictors of albuminuria decline ≥30%. We collected 46 side effects leading to drug discontinuation in 36 patients (2%), with acute kidney injury and urinary tract infection being the most frequent adverse events.

Conclusions: We provide evidence of the anti-proteinuric efficacy of short-term dapagliflozin in the presence of good safety profile in patients with CKD followed in nephrology.