Clinical and Experimental Nephrology最新文献

Background: Erythropoiesis-stimulating agents (ESA) hyporesponsiveness may be linked to malignancy, but studies examining this association are limited. We investigated whether initial ESA hyporesponsiveness and changes in responsiveness may serve as clinical markers reflecting undiagnosed malignancy in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).

Methods: We used data from the BRIGHTEN, a prospective study of NDD-CKD patients with anemia. Initial ESA responsiveness was assessed using the erythropoietin resistance index (ERI-1B), calculated as the ratio of darbepoetin-alfa dose (μg) to hemoglobin concentration (g/dL) at 12 weeks after darbepoetin-alfa initiation. ESA responsiveness trends after 12 weeks were analyzed using a joint latent class model (JLCM). The associations of both initial ESA responsiveness and ESA responsiveness trends after 12 weeks with malignancy development were analyzed using a Cox proportional hazards model.

Results: Of the 1641 patients analyzed, 44 developed new malignancies. Patients with poor ESA response at 12 weeks (ERI-1B > 3.8 μg/g/dL) had a higher incidence of malignancy compared to those with better ESA response (adjusted hazard ratio [HR]: 2.07; 95% confidence interval [CI]: 1.07-4.00). Furthermore, based on the JLCM, patients in the poor response group, characterized by a faster decline in ESA responsiveness after 12 weeks, had a higher risk of malignancy than the good response group (adjusted HR: 2.01; 95% CI: 1.08-3.72).

Conclusion: Both initial ESA hyporesponsiveness and subsequent declines in responsiveness were significantly associated with the development of malignancy in patients with NDD-CKD. ESA hyporesponsiveness may serve as a clinical marker that reflects an increased risk of undiagnosed malignancy.

Background: Early reduction in proteinuria has been validated as a surrogate endpoint for IgA nephropathy (IgAN) in Western trials and is used for accelerated drug approval. However, its applicability to Japanese patients remains unclear. We aimed to evaluate the association between early proteinuria reduction and long-term renal outcomes in Japanese patients with IgAN.

Methods: This retrospective observational study used data from J-CKD-DB-Ex, a real-world database of CKD in Japan. Adult participants with IgAN, baseline urine protein/creatinine ratio (UPCR) ≥ 0.5 g/gCr, and eGFR ≥ 30 mL/min/1.73 m² were included. The exposure was a ≥ 30% UPCR reduction at 9-12 months after the index date (UPCR reduction group), vs participants without such reduction (non-UPCR reduction group). The primary endpoint was a composite of 40% decline in eGFR from baseline or onset of CKD stage G5. Cox proportional hazards and linear mixed-effects models evaluated the association between UPCR reduction, renal events, and eGFR slope.

Results: Among 385 participants (mean observation period 2,040 days), 245 achieved ≥ 30% reductions in UPCR. The UPCR reduction group showed significantly lower cumulative incidence of renal composite events than the non-UPCR reduction group. Annual eGFR decline was slower in the UPCR reduction group than that in the non-UPCR group (-1.9 vs -3.4 mL/min/1.73 m²/year). Greater UPCR reductions were linearly associated with more favorable eGFR slope.

Conclusions: Early proteinuria reduction is associated with decreased risk of renal failure and attenuated eGFR decline in Japanese patients with IgAN, supporting its validity as a surrogate endpoint for renal prognosis.

Background: Proteinuria reduction is considered a potential surrogate endpoint predictive of reflecting long-term kidney prognosis in IgA nephropathy (IgAN), but quantitative evidence in Japanese patients is limited. We aimed to examine the association between short-term proteinuria reduction at 12 months and long-term kidney outcomes in Japan IgA Nephropathy Cohort Study (J-IGACS).

Methods: Participants from J-IGACS were categorized into tertiles based on their 12-month proteinuria-to-baseline proteinuria ratios. The primary outcome was a composite of ≥ 40% estimated glomerular filtration rate (eGFR) decline or initiation of kidney-replacement therapy. Associations between proteinuria ratio and outcomes were assessed using Cox proportional hazards models and restricted cubic splines. Multivariable analyses adjusted for age, sex, baseline eGFR, log-transformed proteinuria, Oxford classification scores, and use of corticosteroids and renin-angiotensin-aldosterone system inhibitors within 12 months.

Results: Among 792 patients, those in the greatest proteinuria reduction had significantly lower risk of the primary endpoint (P for trend < 0.001) and a more favorable eGFR slope. Spline analysis showed a continuous, dose-response association between proteinuria ratio and improved outcomes. These findings remained robust in sensitivity analyses restricted to patients likely qualifying for clinical trials. The results showed that patients with lower proteinuria ratios tended to have slower rates of eGFR decline (P for trend < 0.001).

Conclusion: Proteinuria reduction within the first-year post-diagnosis is independently associated with lower risk of adverse kidney outcomes and a slower decline in kidney function in patients with IgAN. These results support the use of proteinuria reduction as a surrogate endpoint in both clinical trials and disease management.

Background: Effectively managing a large numbers chronic kidney disease (CKD) cases requires collaboration between nephrologists and non-nephrologists. In 2024, the Japan physicians association conducted a third nationwide questionnaire survey on managing CKD. This study aimed to clarify the differences in managing CKD between nephrologists and non-nephrologists and identify remaining issues by comparing them with past surveys.

Method: In the 2024 surveys, 1003 general practitioners voluntarily participated and answered 20 questions about CKD care and treatment. They were divided into 2 groups: 835 non-nephrologists and 168 nephrologists, and the differences were analyzed. Furthermore, the 2024 survey results were compared with those from the 2013 and 2019 surveys.

Results: The use of CKD guidelines was significantly lower among non-nephrologists than nephrologists (55%/21% and 86%/60%, respectively; p < 0.001), and as in the past 2 surveys (p < 0.001). Estimated glomerular filtration rate assessment was widespread at 95%; nevertheless, 34% of non-nephrologists measured quantitative proteinuria compared to 82% of nephrologists (p < 0.001). This prevalence decreased with each survey and with the age of the non-nephrologists. While 75% of nephrologists prescribed renin-angiotensin system inhibitors for patients with CKD and hypertension, considering their renoprotective effects, 45% of non-nephrologists answered it (p < 0.001). While 61% of non-nephrologists prescribed sodium-glucose co-transporter 2 inhibitors to patients with CKD, regardless of diabetes complications, compared to 83% of nephrologists (p < 0.001).

Conclusion: The quality of CKD management by non-nephrologists partially improved in the past decade; however, the low use of guidelines and implementation of quantitative proteinuria measurements among non-nephrologists needs to be addressed in future.

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: 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.

Background: Exercise therapy is recommended for patients with chronic kidney disease (CKD), but evidence for its effectiveness in older adults with pre-dialysis CKD is limited.

Methods: This single-center randomized controlled trial examined the effects of a six-month home-based exercise program with monthly counseling in 29 patients aged ≥ 65 years with stage 3-5 pre-dialysis CKD. Participants were randomly assigned to an exercise group (n = 15) or control group (n = 14). Primary outcomes were physical function, measured by 6-min walk distance (6MWD), and health-related quality of life (HRQOL), assessed using the Kidney Disease Quality of Life Short Form (KDQOL-SF). Secondary outcomes included depressive symptoms, nutritional status, and renal function.

Results: 6MWD significantly improved in the exercise group, while no significant change was observed in the control group (p < 0.05). The change in 6MWD was significantly greater in the exercise group than in the control group (p < 0.05). In KDQOL-SF, the role-physical score significantly improved in the exercise group and declined in the control group (p < 0.05). No significant changes were observed in secondary outcomes.

Conclusions: A six-month home-based exercise program with counseling improved physical function and HRQOL in older patients with pre-dialysis CKD.

Background: Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors have been used for the treatment of anemia in patients with chronic kidney disease not receiving dialysis since 2020. In September 2020, the Japanese Society of Nephrology published recommendations for the appropriate use of HIF-PH inhibitors, which emphasized monitoring iron indices. However, real-world adherence to these recommendations remains unclear.

Methods: We retrieved the data of new users of erythropoietin-stimulating agents (ESAs) or HIF-PH inhibitors from a large Japanese claims database (DeSC, Tokyo, Japan) between 2018 and 2022. Adherence to iron testing before and after the treatments was analyzed using modified Poisson regression and Cox models. Facility-level variations were assessed via mixed-effects models.

Results: We identified 105,346 patients who had a new prescription of ESAs (n = 86,263) or HIF-PH inhibitors (n = 19,083) and did not have kidney failure with replacement therapy. The proportion of HIF-PH inhibitor use increased from 3.6% in 2020 to 42.7% in 2022. During the study period, testing frequency for serum iron, serum TIBC or UIBC, and ferritin ranged from 57.2-59.8%, 39.2-42.8%, and 50.6-52.6%, respectively. Multivariate analysis showed that adherence to testing was significantly higher in university hospitals, Diagnosis Procedure Combination-affiliated DPC hospitals, and non-DPC hospitals compared with clinics. A similar tendency was observed in testing after the index date.

Conclusions: The type of facility was the primary determinant of adherence to the recommendation for iron indices testing before the initiation of ESAs or HIF-PH inhibitors. Targeted educational interventions in low-adherence settings may help improve adherence rates and optimize patient care.