Clinical Kidney Journal最新文献

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.

Background: Dipeptidyl peptidase 4 inhibitors (DPP4is) are considered safe for use in patients with diabetes mellitus and kidney dysfunction. We explored whether usage of DPP4is in patients who recovered from dialysis-requiring acute kidney injury (AKI) could reduce the risk of future cardiac and kidney events.

Methods: We used the TriNetX platform to investigate whether the use of DPP4is in diabetes mellitus patients within 90 days of discharge from acute kidney disease could reduce the risk of all-cause mortality, major adverse kidney events (MAKEs), major adverse cardiovascular events (MACEs), and re-dialysis. The patients were followed for 5 years or until the occurrence of significant outcomes, with cohort data collected from 1 January 2016 to 30 September 2022.

Results: The cohort utilizing DPP4is comprised 7348 patients with acute kidney disease, while the control group encompassed 229 417 individuals. After applying propensity score matching, 7343 patients (age 66.2 ± 13.4 years; male, 49.9%) who used DPP4is showed a significant reduction in the risk of all-cause mortality [adjusted hazard ratio (aHR) 0.89; E-value 1.50 , MAKEs (aHR 0.86; E-value 1.59), MACEs (aHR 0.91; E-value 1.44), and re-dialysis (aHR 0.73; E-value 2.10) after a median follow-up of 2.4 years.

Conclusions: We demonstrated that in diabetes mellitus patients concurrently experiencing acute kidney disease, DPP4i usage could decrease the risk of mortality, MAKEs, MACEs, and re-dialysis. These findings emphasize the pivotal role of tailored treatment strategies involving DPP4i for acute kidney disease patients.

The management of CKD in older patients presents a significant challenge in modern medicine. As the global population ages, the prevalence of CKD among older adults is increasing, which demands effective and safe treatment strategies. The introduction of sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists has revolutionized the treatment of CKD, offering potential benefits beyond traditional therapies. However, their use in the older population raises essential questions about safety and efficacy, given the unique physiological changes and comorbidities associated with aging. In this CKJ controversy paper, Roberto Minutolo (PRO) and Sophie Liabeuf (CON) debate on the use of SGLT2 inhibitors and GLP-1 receptor agonists in older patients with CKD. Roberto Minutolo advocates the benefits of these medications, highlighting their role in improving cardiovascular outcomes and slowing CKD progression in older patients. He emphasizes the importance of personalized treatment plans based on the patient's cardio-renal risk profile and preferences. In contrast, Sophie Liabeuf expresses concerns about the safety of these drugs in older adults, citing risks such as fractures, acute kidney injury, and urinary tract infections. She argues that treatment decisions should be guided by patient frailty rather than chronological age, as frail individuals are more vulnerable to adverse drug effects. Both contenders agree on the need for more inclusive clinical trials to better understand the impact of these treatments on older populations. While Roberto Minutolo and Sophie Liabeuf present differing perspectives on the use of SGLT2 inhibitors and GLP-1 receptor agonists in older patients with CKD, their views can be seen as complementary rather than strictly opposing. Minutolo's focus on the benefits of these drugs underscores their potential to improve outcomes. Liabeuf's emphasis on caution and the consideration of frailty highlights the need for careful patient assessment. Both agree on the importance of personalized treatment and the inclusion of older patients in future clinical trials, suggesting a shared goal of optimizing care for this vulnerable population. Their debate underscores the complexity of treatment decisions and the necessity of balancing risks and benefits in managing CKD in older adults.

Background: Serum magnesium disturbances are common in patients with cardiovascular disease (CVD). However, the well-established link between low serum magnesium and nutritional or inflammatory disorders has limited its consideration as a non-traditional risk factor for mortality. This study aims to elucidate the relationship between serum magnesium concentrations and mortality due to fatal heart failure (HF), coronary heart disease (CHD) and stroke in non-dialysis patients with chronic kidney disease (CKD) stages 4 and 5.

Methods: A cohort of 1271 non-dialysis patients with CKD stages 4 and 5 was followed from 2008 to 2018. Patients with prior major adverse cardiovascular events (MACE) were excluded. Serum magnesium levels were stratified into tertiles and the primary outcomes were incidence rates of fatal HF, CHD and stroke. Secondary outcomes included composite MACE and all-cause mortality. Hazard ratios (HRs) were calculated using multivariate Cox regression, adjusting for demographics, comorbidities and biochemical parameters. E-values were used to assess the robustness of the results.

Results: Over the 10-year follow-up, 186 patients died. Higher serum magnesium levels were significantly associated with reduced mortality risk from HF [HR 0.49 (95% CI 0.27-0.89) for T2; HR 0.31 (95% CI 0.16-0.60) for T3] compared with the lowest tertile. Similar trends were observed for CHD and stroke mortality. The incidence rate of MACE per 1000 person-years was reduced from 68.2 in tertile 1 to 26.2 in tertile 2 and 16.8 in tertile 3. Secondary endpoints, including all-cause mortality and composite MACE, followed trends similar to the primary outcomes.

Conclusions: Higher serum magnesium concentrations were associated with lower risks of death from fatal HF, CHD and stroke in non-dialysis patients with CKD stages 4 and 5.

Background: Chronic kidney disease (CKD) is mainly managed in primary care, but detailed information on these patients is limited. This study describes CKD patients and the disease management and referrals by general practitioners (GPs) in Denmark in order to identify opportunities for improved care.

Methods: Patients with CKD, defined by at least two abnormal estimated glomerular filtration rate (eGFR) or urinary albumin/creatinine ratio (UACR) measurements ≥90 days apart during 2019-2020, were followed until May 2023 utilizing electronic health records.

Results: Among 1316 patients with one abnormal eGFR or UACR test, 993 (75%) had a second abnormal test within a median of 10.8 months, which confirmed CKD. Most patients (62%) were G-stage 3a, 89% had cardiovascular disease and 34% had diabetes. A UACR test was performed in 52% of patients around time of index. The use of renin-angiotensin-aldosterone system inhibitors was high (67%), whereas sodium-glucose cotransporter 2 inhibitors was low at inclusion (5%), although increasing during follow-up (15%). Patients had a median of 13.5 GP contacts/year, 1-2 eGFR and 0-1 UACR tests/year, and only 2.7% were referred to a nephrologist. The median decline in eGFR was modest; however, 15% experienced a drop of >5.0 mL/min/1.73 m² during 3-years of follow-up.

Conclusions: The findings indicate a high likelihood of CKD following one abnormal measurement. CKD patients constitute a significant burden to primary care with frequent GP contacts, yet more focus on UACR testing and new treatment adaptation to improve CKD prognosis is warranted.