Clinical and Experimental Nephrology最新文献

Background: Zinc deficiency is widely recognized as a cause of anemia, but no studies have clarified the impact of zinc deficiency on achieving target hemoglobin levels in patients undergoing peritoneal dialysis (PD) and receiving high-dose erythropoiesis-stimulating agent (ESA) therapy. This study aimed to investigate the relationship between zinc deficiency and ESA-hyporesponsive anemia in patients on PD.

Methods: This cross-sectional study included 164 patients on PD aged ≥ 18 years. The target hemoglobin level was 11-13 g/dL. ESA dosage was categorized as low-dose (< 120 µg/month) or high-dose (≥ 120 µg/month), while zinc deficiency was defined as a serum zinc level < 60 µg/dL. A logistic regression model was used to calculate the odds ratio (OR) for achieving the target hemoglobin level.

Results: The proportion of patients achieving the target hemoglobin level was 48.2% in the low-dose ESA and non-zinc-deficient group, and 12.2% in the high-dose ESA and zinc-deficient group. Compared with the low-dose ESA and non-zinc-deficient group, the adjusted OR for achieving the target hemoglobin level was significantly lower in the high-dose ESA and zinc-deficient group (OR: 0.19, 95% confidence interval 0.05-0.72). Stratified analyses based on serum albumin, serum C-reactive protein, and transferrin saturation did not change the association between the high-dose ESA and zinc-deficient group and the achievement of the target hemoglobin level.

Conclusion: Zinc deficiency in patients on PD is a significant barrier to achieving the target hemoglobin level, and serum zinc levels should be routinely monitored in patients with ESA-hyporesponsive anemia.

Background: Clinical practice guidelines do not recommend tonsillectomy combined with steroid pulse therapy (TSP) as the initial treatment of severe IgA nephropathy (IgAN) in children. Therefore, the long-term prognosis following TSP is unknown in IgAN children with heavy proteinuria.

Methods: This retrospective study aimed to determine the long-term outcome of children with IgAN and heavy proteinuria (urinary protein-to-creatinine ratio, ≥ 1.0 g/g) following TSP as the initial treatment. The primary endpoint was the probability of achieving treatment-free clinical remission (CR: disappearance of both hematuria and proteinuria) without developing kidney complications at the last follow-up.

Results: After initiating TSP in 43 patients (median age, 10.4 years), CR was achieved in 41 patients (95%) at a median of 9.6 months. During the observation period (median, 7.5 years), four patients experienced proteinuria recurrence that required additional therapy. At the last follow-up (median age, 18.2 years), 37 patients (86%) achieved treatment-free CR without developing kidney complications (favorable group), whereas six patients received a renin-angiotensin system inhibitor for persistent proteinuria (unfavorable group). The age and proportion of glomeruli with crescents at IgAN diagnosis were significantly lower in the favorable group than in the unfavorable group. Multivariable analysis showed that a younger age at IgAN diagnosis (< 12.2 years) was an independent predictive factor for favorable outcomes. There were no serious adverse events and no significant negative changes in the anthropometric outcomes.

Conclusions: Initial treatment with TSP may result in treatment-free CR in children with IgAN and heavy proteinuria, particularly in patients diagnosed at a young age.

Background: Mean corpuscular volume (MCV) is routinely measured in patients with chronic kidney disease (CKD) and anemia; however, its prognostic significance, particularly in the context of erythropoiesis-stimulating agent (ESA) therapy, remains unclear.

Methods: We conducted a post hoc analysis of the BRIGHTEN study, a multicenter, prospective trial that enrolled 1219 ESA-naïve patients with non-dialysis-dependent CKD who initiated darbepoetin alfa. Patients were categorized based on changes in MCV from baseline to week 16 as either increased or decreased. The primary outcome was renal function decline, defined as the initiation of dialysis, kidney transplantation, ≥ 50% reduction in estimated glomerular filtration rate (eGFR), or an eGFR ≤ 6 mL/min/1.73 m² within 96 weeks.

Results: MCV decreased in 778 (63.8%) patients during the study period. Changes in MCV were not correlated with baseline MCV values or ESA responsiveness. Over a mean follow-up of 2.46 ± 0.78 years, renal function decline occurred in 304 (39.1%) and 140 (31.7%) patients in the decreased and increased MCV groups, respectively. After adjusting for age, sex, baseline eGFR, albumin, high-sensitivity CRP, proteinuria, ferritin, transferrin saturation and ESA responsiveness, increased MCV remained independently associated with a reduced risk of renal function decline (adjusted hazard ratio 0.67; 95% confidence interval 0.53-0.85; p < 0.001).

Conclusion: In ESA-naïve patients with non-dialysis-dependent CKD, an increase in MCV following ESA treatment was associated with a significantly lower risk of renal function decline. Monitoring MCV dynamics may serve as a simple, adjunctive tool for risk stratification and individualized CKD management.

Background: Proteinuria reduction is an established surrogate endpoint for IgA nephropathy (IgAN) progression in international trials, but evidence in Japanese populations is scarce. We aimed to assess the association between early changes in proteinuria and long-term kidney outcomes in a large, real-world cohort of Japanese patients with IgAN.

Methods: This nationwide, multicenter cohort study utilized the Japan Chronic Kidney Disease Database (J-CKD-DB) data. We analyzed 1,039 IgAN patients (mean age 48.8 years; 46.0% women), categorized by dipstick proteinuria change at 9 ± 1 months from baseline: a reduction group (≥1-step improvement) and a non-reduction group (stable or worsened). The primary outcome was total eGFR slope; secondary was a composite kidney event (≥40% eGFR decline or eGFR < 15 mL/min/1.73 m²).

Results: The mean baseline eGFR was 56.8 (±27.7) mL/min/1.73 m². During a median follow-up of 1,357 days, the mean annual eGFR slope in the reduction group was -0.13 mL/min/1.73 m² (95% CI, -0.37 to 0.11), compared to -2.73 mL/min/1.73 m² (95% CI, -2.96 to -2.49) in the non-reduction group. In multivariable adjustment for baseline covariates, the hazard ratio for the composite kidney event in the reduction group was significantly lower compared to the non-reduction group was 0.79 (95% CI, 0.63-0.99).

Conclusions: In this large, real-world Japanese cohort, early dipstick proteinuria reduction was significantly associated with both a slower long-term eGFR decline and a lower risk of major kidney events. These findings may support the use of early proteinuria reduction as a surrogate endpoint for clinical trials and regulatory evaluation of IgA nephropathy in Japan.

Background: Although the SARS-CoV-2 Omicron variant demonstrates lower mortality than previous variants in the general population, its impact on patients with end-stage kidney disease (ESKD) remains concerning. Substantial mortality has been reported in patients with ESKD during the Omicron period; however, comparing this with influenza mortality could provide insights into COVID-19's true impact in this high-risk population.

Methods: Using the National Database of Health Insurance Claims of Japan, we conducted a retrospective cohort study of hemodialysis patients diagnosed with COVID-19 during the Omicron period (January 2022-March 2023) or influenza (September 2017-March 2023). The primary outcome was 30-day all-cause mortality. Overlap weighting based on propensity scores balanced confounding factors.

Results: We identified 53,047 COVID-19 and 35,808 influenza cases. After overlap weighting, the 30-day mortality rates were 3.4% for COVID-19 and 1.8% for influenza (hazard ratio [HR] 1.61 [95% CI 1.47, 1.77]). In subgroup analyses stratified by age, HRs were comparable across all age groups (20-49 years: 1.59 [0.81, 3.13]; 50-59 years: 1.43 [0.94, 2.17]; 60-69 years: 1.45 [1.15, 1.84]; 70-79 years: 1.68 [1.43, 1.96]; ≥ 80 years: 1.66 [1.45, 1.89]). The absolute risk differences (per 1,000 patients) across age groups were 1.7, 2.6, 6.2, 16.2, and 28.9 deaths, respectively.

Conclusions: In this nationwide study, COVID-19 Omicron variant was associated with significantly higher mortality than influenza in hemodialysis patients. Age-stratified analyses showed consistent relative risks but progressively larger absolute risk differences in older patients.

Background: The validity of the International Classification of Diseases 10th Revision (ICD-10) codes for chronic kidney disease (CKD) in Japan have not been evaluated. In this study we evaluated the validity of CKD-related ICD-10 codes in Japan.

Methods: This retrospective cohort study used the JMDC hospital-based database, which comprises claims and laboratory data from over 1,000 medical institutions in Japan. Patients who underwent two serum creatinine measurements between April 2014 and August 2022 were identified; the second measurement was obtained 90-365 days after the first. The estimated glomerular filtration rate (eGFR) was calculated. CKD was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria: an eGFR < 60 mL/min/1.73 m² for both measurements. Markers of kidney damage such as albuminuria were unavailable. Patients assigned CKD-related ICD-10 codes (N183, N184, N185, N189, N19, E102, E112, E142, and I120) within 365 days of the initial serum creatinine measurement were identified. Subsequently, the positive predictive value (PPV), sensitivity, specificity, and negative predictive value (NPV) were calculated.

Results: Among the 618,208 included patients, 59,139 were assigned CKD-related ICD-10 codes and 172,657 met the KDIGO criteria. The overall PPV, sensitivity, specificity, and NPV were 57.9%, 19.8%, 94.4%, and 75.2%, respectively. In contrast, the PPVs of N183, N184, N185, and N189 exceeded 80%.

Conclusions: In Japan, the PPV of the ICD-10 codes for CKD was 57.9%, marginally lower than values reported in the United States (86.1%) and Canada (60.1%). Several ICD-10 codes may be useful for identifying patients with CKD, despite their limited sensitivity.

Background: Zinc-α2-glycoprotein (ZAG) is an adipokine, which may act locally to regulate adipocyte metabolism. Downregulation of ZAG expression in obesity has been reported in obesity in both mice and humans. In contrast, other studies revealed that serum ZAG levels were positively associated with renal dysfunction. We investigated whether serum ZAG levels serve as a biomarker for renal impairment in a general population, both cross-sectionally and longitudinally.

Methods: A total of 223 residents (85 men and 138 women, mean age 67.1 ± 9.7 years old) underwent health examinations in 2011. Baseline fasting blood samples were collected, including measurement of serum ZAG. Participants were followed annually for 13 years.

Results: Mean serum ZAG levels were 49.2 ± 13.7 μg/mL in males, and 41.7 ± 9.0 μg/mL in females. In univariate analysis, ZAG levels were significantly associated with male gender (p = 0.005), estimated glomerular filtration rate (eGFR p = 0.004, inversely), smoking habit (p = 0.031), and medication for hyperlipidemia (p = 0.024 inversely). In multiple logistic regression analysis, eGFR (p = 0.002, inversely), male gender (p = 0.003), and medication for hyperlipidemia (p = 0.038 inversely) remained significantly and independently associated with serum ZAG at baseline. During follow-up, 31 subjects developed chronic kidney diseases (CKD). However, baseline ZAG was not significantly associated with incident CKD over 13 years.

Conclusions: Serum ZAG levels were independently associated with renal function and may represent a novel biomarker of renal dysfunction in a general population. However, ZAG did not predict long-term CKD development.

Objective: This study aimed to investigate the role of B7-H3-an immune checkpoint implicated in inflammation and vascular remodeling-in uremic vascular calcification (UVC), particularly its effects on calcium deposition, vascular smooth muscle cell (VSMC) phenotype, and VSMC-macrophage crosstalk.

Methods: An in vitro UVC model was established using β-glycerophosphate (β-GP) treated human aortic VSMCs (HA-VSMCs). B7-H3 expression was silenced using siRNA. Calcification was assessed by Alizarin Red S staining, ALP activity, and calcium content assays. VSMCs phenotype switching was evaluated by Western blot for contractile and osteogenic markers. Macrophage recruitment, adhesion, and polarization (M1/M2) were assessed using THP-1 cells in co-culture systems and analyzed by qRT-PCR and flow cytometry. The effect of macrophage polarization on VSMCs calcification was investigated in the presence or absence of B7-H3 knockdown.

Results: β-GP treatment induced HA-VSMC calcification, osteogenic differentiation, and upregulated B7-H3 expression. Silencing B7-H3 attenuated calcification, restored contractile markers, and reduced osteogenic markers in VSMCs. B7-H3 knockdown also suppressed the recruitment and adhesion of macrophages to HA-VSMCs, inhibited M1 polarization of co-cultured macrophages, and promoted their shift toward the M2 phenotype. Furthermore, silencing B7-H3 mitigated M1 macrophage-induced VSMC calcification and enhanced the protective effects of M2 macrophages.

Conclusion: B7-H3 promotes UVC directly by inducing osteogenic transformation of VSMCs and indirectly by enhancing macrophage recruitment and favoring pro-calcific M1 polarization. Thus, targeting B7-H3 may represent a promising therapeutic strategy to mitigate UVC.

Background: Post-transplant malignancies are the leading causes of death in patients after kidney transplant (KT) and significantly contribute to death with a functioning graft (DWFG). The incidence of such malignancies is 3-5 times higher than in the general population, with various reported risk factors. However, the association between ABO-incompatible KT and post-transplant malignancies has not yet been thoroughly investigated. We evaluated the association between ABO incompatibility and the development of malignancies in living-donor KT recipients.

Methods: This study included 605 of 643 patients who underwent living-donor KT at six facilities in the Tohoku region of Japan, part of the Michinoku Renal Transplant Network (MRTN), between May 1998 and November 2021, with exclusion of those with missing data. The primary endpoint was the incidence of first post-transplant malignancy. Patients were divided into ABO-compatible (ABOc) and ABO-incompatible (ABOi) groups, and analyses were conducted to compare these groups.

Results: The mean patient age was 47.1 years. The ABOc group included 464 patients (76.7%), whereas the ABOi group included 141 patients (23.3%). During the observation period, 67 patients (11.1%) developed post-transplant malignancies, with gastrointestinal and genitourinary cancers being the most common (median observation period, 77.0 months). There was no significant difference in the incidence of the first post-transplant malignancy between the two groups. Multivariate analysis identified age as the only factor associated with the development of a first post-transplant malignancy.

Conclusion: This study demonstrates ABOi living-donor KT is not associated with an increased risk of post-transplant malignancy in the mid to long term.