Blood Hemoglobin Concentrations and the Incidence of Lower Extremity Peripheral Arterial Disease in Patients Undergoing Hemodialysis: 10-Year Outcomes of the Q-Cohort Study.

BACKGROUND: Lower extremity peripheral arterial disease is a potentially lethal cardiovascular complication in patients undergoing hemodialysis. Anemia is a risk factor for cardiovascular disease among the hemodialysis population. However, whether blood hemoglobin concentration is associated with the risk of peripheral arterial disease progression in this population remains undetermined. METHODS AND RESULTS: This is an extension of a 4-year multicenter, prospective, observational cohort study to 10 years. A total of 3504 Japanese patients undergoing maintenance hemodialysis were recruited between 2006 and 2007. The primary exposure was blood hemoglobin concentration at baseline. The main outcome was the first-ever incidence of major adverse limb events (MALE), composed of endovascular treatment, bypass surgery, and amputation. Multivariable-adjusted Cox proportional hazards model, Fine-Gray subdistribution hazards model, restricted cubic spline analysis, and restricted mean survival time analysis were used to determine the association of blood hemoglobin concentration with the incidence of MALE. During a median follow-up of 8.0 years, 257 patients experienced MALE. A Cox proportional hazards model showed that the risk of MALE in patients with blood hemoglobin concentrations <10.0 g/dL was significantly higher than in patients with concentrations of 11.0 to 11.9 g/dL, even after adjusting for confounding factors. In contrast, elevated hemoglobin concentration (≥12.0 g/dL) was not significantly associated with increased risk of MALE. Similar associations were observed when the Fine-Gray subdistribution regression model was used by setting all-cause mortality as the competing risk. CONCLUSIONS: A low blood hemoglobin concentration is an independent risk factor for peripheral arterial disease progression in patients undergoing maintenance hemodialysis.

Vascular Calcification Is Accelerated by Hyponatremia and Low Osmolality.

BACKGROUND: Hyponatremia, frequently observed in patients with chronic kidney disease, is associated with increased cardiovascular morbidity and mortality. Hyponatremia or low osmolality induces oxidative stress and cell death, both of which accelerate vascular calcification (VC), a critical phenotype in patients with chronic kidney disease. Whether hyponatremia or low osmolality plays a role in the pathogenesis of VC is unknown. METHODS: Human vascular smooth muscle cells (VSMCs) and mouse aortic rings were cultured in various osmotic conditions and calcifying medium supplemented with high calcium and phosphate. The effects of low osmolality on phenotypic change and oxidative stress in the cultured VSMCs were examined. Microarray analysis was conducted to determine the main signaling pathway of osmolality-related VC. The transcellular sodium and calcium ions flux across the VSMCs were visualized by live imaging. Furthermore, the effect of osmolality on calciprotein particles (CPPs) was investigated. Associations between arterial intimal calcification and hyponatremia or low osmolality were examined by a cross-sectional study using human autopsy specimens obtained in the Hisayama Study. RESULTS: Low osmolality exacerbated calcification of the ECM (extracellular matrix) of cultured VSMCs and mouse aortic rings. Oxidative stress and osteogenic differentiation of VSMCs were identified as the underlying mechanisms responsible for low osmolality-induced VC. Microarray analysis showed that low osmolality activated the Rac1 (Ras-related C3 botulinum toxin substrate 1)-Akt pathway and reduced NCX1 (Na-Ca exchanger 1) expression. Live imaging showed synchronic calcium ion efflux and sodium ion influx via NCX1 when extracellular sodium ion concentrations were increased. An NCX1 inhibitor promoted calcifying media-induced VC by reducing calcium ion efflux. Furthermore, low osmolality accelerated the generation and maturation steps of CPPs. The cross-sectional study of human autopsy specimens showed that hyponatremia and low osmolality were associated with a greater area of arterial intimal calcification. CONCLUSIONS: Hyponatremia and low osmolality promote VC through multiple cellular processes, including the Rac1-Akt pathway activation.

Disturbance in the potential cardiovascular-bone-skeletal muscle axis and morbidity and mortality in patients undergoing haemodialysis: the Q-Cohort Study.

Background: Disturbances in the cardiovascular system, bone and skeletal muscle are independent risk factors for death among patients receiving haemodialysis (HD). However, the combined impact of disorders of these three organs on morbidity and mortality is unclear in the HD population. Methods: A total of 3031 Japanese patients on maintenance HD were prospectively followed. The outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and bone fracture. Patients were divided into four groups (G1-G4) according to the baseline number of diseased organs represented as histories of cardiovascular disease and bone fractures and the presence of low skeletal muscle mass as follows: G1, no organ; G2, one organ; G3, two organs; G4, three organs. Multivariable-adjusted survival models were used to analyse associations between the number of diseased organs and outcomes. Results: During a 4-year follow-up, 499 deaths, 540 MACE and 140 bone fractures occurred. In the Cox proportional hazards model, the risk for all-cause mortality was significantly higher in G2, G3 and G4 than in G1 as the reference {hazard ratio: G2, 2.16 [95% confidence interval (CI) 1.65-2.84], G3, 3.10 [95% CI 2.27-4.23] and G4, 3.11 [95% CI 1.89-5.14]}. Similarly, the risks for developing MACE and bone fractures were significantly elevated as the number of organ disorders increased. Conclusions: Multiple disorders of the cardiovascular-bone-skeletal muscle axis are strong predictors of morbidity and mortality in patients undergoing HD.

Combined evaluation of glomerular phospholipase A2 receptor and immunoglobulin G subclass in membranous nephropathy.

Background: Phospholipase A2 receptor (PLA2R) is a major target antigen in idiopathic membranous nephropathy (MN). Anti-PLA2R antibodies are mainly of the immunoglobulin G (IgG) subclass IgG4, although other IgG subclass depositions in glomeruli may also be detected. However, the importance of the subclass of the IgG deposit has not been proven. Thus we investigated clinical findings from patients with idiopathic MN in relation to glomerular PLA2R deposition and IgG subclass. Methods: We enrolled 132 Japanese patients with biopsy-proven idiopathic MN in a multicentre retrospective observational study. We investigated the complete remission rate as the primary outcome and the development of end-stage kidney disease (ESKD) as the secondary outcome in relation to glomerular PLA2R deposition. Moreover, we evaluated prognostic factors, including glomerular IgG subclass, in the PLA2R-positive group. Results: The percentage of cases with glomerular PLA2R deposition was 76.5% (n = 101). The first complete remission rate of the PLA2R-positive group was worse than that of the PLA2R-negative group (logrank test P < .001). ESKD incidence did not significantly differ between the glomerular PLA2R-negative and PLA2R-positive MN groups (logrank test P = .608). In the PLA2R-positive group, higher PLA2R intensities and IgG2 staining were associated with a poorer first complete remission rate (logrank test P < .001 and P = .032, respectively). Cox proportional hazards analysis also showed that strong PLA2R deposition and positive IgG2 staining were significantly associated with a failure to reach complete remission [hazard ratio 2.09 (P = .004) and 1.78 (P = .030), respectively]. Conclusions: Our results suggest that intense glomerular PLA2R and IgG2 positivity predict a poor proteinuria remission rate in idiopathic MN.

Very Slowly Progressive Microscopic Polyangiitis: Comparative Analysis with Rapidly Progressive Forms.

Microscopic polyangiitis (MPA) is predominantly characterized by rapidly progressive glomerulonephritis (RPGN) associated with myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA). Nonetheless, up to 30% of cases of ANCA-associated vasculitis (AAV) may exhibit a more indolent progression toward renal failure, an aspect less frequently discussed and understood in medical literature. This study seeks to clarify the clinical and pathological distinctions between the slowly and rapidly progressive forms of MPA, thereby enhancing understanding of their distinct pathogeneses and treatment responses. We conducted a comparative analysis of two patients diagnosed with MPA under the 2022 American College of Rheumatology/the European Alliance of Associations for Rheumatology (ACR/EULAR) classification. Evaluations included laboratory tests such as serum creatinine levels, serology for MPO-ANCA, and renal biopsies. Patient 1 exhibited a mere 1.07% decrease in estimated glomerular filtration rate (eGFR) over 6 months, significantly below the RPGN threshold, and demonstrated sclerotic glomerular pathology without active inflammation. This patient also showed lower levels of MPO-ANCA, Birmingham Vasculitis Activity Score (BVAS), and C-reactive protein. Conversely, Patient 2 experienced an 89.9% reduction in eGFR over the same timeframe, accompanied by acute systemic inflammation. The comparative clinical analysis of these cases illuminates clear differences in disease activity. Slowly progressive MPA is marked by lesser disease activity that fosters chronic inflammation, leading to a more gradual decline in renal function. Early diagnosis, facilitated by initial measurements of MPO-ANCA, can enhance disease management and improve patient outcomes.

Association Between Disturbed Serum Phosphorus Levels and QT Interval Prolongation.

Introduction: QT interval prolongation is a risk factor for fatal arrhythmias and other cardiovascular complications. QT interval prolongation in patients on hemodialysis (HD) is not well understood. Hypocalcemia is a suspected, but poorly verified etiology in these patients, and the association between serum phosphorus levels and QT interval prolongation is unknown. We sought to determine the prevalence of QT interval prolongation in patients on HD and to verify the association between predialysis serum calcium (Ca) and phosphate (P) levels and QT interval prolongation. Methods: A cross-sectional study was conducted on adult patients on maintenance HD who were enrolled in the Japanese Society for Dialysis Therapy and Renal Data Registry 2019. After assessing patient characteristics, linear regression analysis was performed with predialysis serum Ca and P levels as exposures and a rate-corrected QT (QTc) interval as the outcome. Results: A total of 204,530 patients were analyzed with a mean QTc of 451.2 (standard deviation, 36.9) ms. After multivariable analysis, estimated change in QTc (coefficients; 95% confidence interval) per 1 mg/dl increase in serum Ca and P was -2.02 (-3.00 to -1.04) and 5.50 (3.92-7.09), respectively. In the restricted cubic spline curve, estimated change in QTc increased with lower values of serum Ca. The correlation between serum P and QTc showed a U-shaped curve. Conclusion: Decreased serum Ca levels and decreased and increased serum P levels may be associated with QT interval prolongation in patients on maintenance HD.

Associations between the Serum Triglyceride Level and Kidney Outcome in Patients with Chronic Kidney Disease: The Fukuoka Kidney disease Registry Study.

AIMS: Hypertriglyceridemia is a risk factor for chronic kidney disease (CKD). However, whether or not it predicts the risk of CKD progression is unknown. This study evaluated the association between serum triglyceride (TG) levels and kidney disease progression in patients with non-dialysis-dependent CKD. METHODS: The Fukuoka Kidney disease Registry (FKR) study was a multicenter, prospective longitudinal cohort study. In total, 4,100 patients with CKD were followed up for 5 years. The primary outcome was the incidence of CKD progression, defined as a ≥ 1.5-fold increase in serum creatinine level or the development of end-stage kidney disease. The patients were divided into quartiles according to baseline serum TG levels under non-fasting conditions: Q1 ＜87 mg/dL; Q2, 87-120 mg/dL; Q3, 121-170 mg/dL, and Q4 ＞170 mg/dL. RESULTS: During the 5-year observation period, 1,410 patients met the criteria for CKD progression. The multivariable-adjusted Cox proportional hazards model showed a significant association between high serum TG level and the risk of CKD progression in the model without macroalbuminuria as a covariate (multivariable hazard ratio[HR] for Q4 versus Q1, 1.20; 95% CI, 1.03-1.41; P=0.022), but the significance disappeared after adjusting for macroalbuminuria (HR for Q4 versus Q1, 1.06; 95% CI, 0.90-1.24; P=0.507). CONCLUSIONS: The present findings suggest that individuals with high serum TG levels are more likely to develop CKD progression than those without; however, whether or not higher serum TG levels reflect elevated macroalbuminuria or lead to CKD progression via elevated macroalbuminuria is unclear.

Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database.

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (ß = -0.609, p = .039; ß = -2.298, p < .001; ß = -0.936, p = .048; ß = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.

Evaluating the associations between compliance with CKD guideline component metrics and renal outcomes.

Understanding the association between compliance to the Chronic Kidney Disease (CKD) guidelines in real-world clinical settings and renal outcomes remains a critical gap in knowledge. A comprehensive analysis was conducted using data from a national, multicenter CKD registry. This study included 4,455 patients with an estimated glomerular filtration rate (eGFR) measurement on the index date and eight additional metrics recorded within six months. These metrics comprised serum electrolyte levels, low-density lipoprotein cholesterol, hemoglobin, and the use of renin-angiotensin system inhibitors. The primary outcome was a composite of renal events, defined by a decline in eGFR to < 15 mL/min/1.73 m2 or a reduction of ≥ 30% in eGFR, confirmed by follow-up tests. Over a median follow-up of 513 days, 838 renal events were observed. High serum potassium levels (> 5.4 mmol/L) were associated with increased event rates compared to lower levels. Similarly, low serum sodium-chloride levels (< 33) correlated with higher event rates. Usage of renin-angiotensin system inhibitors, low serum calcium (< 8.4 mg/dL), and high uric acid levels (> 7.0 mg/dL) were also linked to increased events. Conversely, higher hemoglobin levels (≥ 13 g/dL) were associated with lower event rates. Compliance to guidelines, categorized into quartiles based on the number of met metrics, revealed a significantly reduced risk of events in the highest compliance group (meeting 8 metrics) compared to the lowest (0-5 metrics). Compliance to CKD guidelines in clinical practice is significantly associated with improved renal outcomes, emphasizing the need for guideline-concordant care in the management of CKD.

Impact of Age on Prescribing Patterns of Cardiovascular Medications in Older Japanese Patients with Non-Dialysis-Dependent Chronic Kidney Disease: A Cross-Sectional Study.

AIM: Older patients with chronic kidney disease (CKD) are more likely to be excluded from clinical trials. This exclusion affects the quality of cardiovascular disease (CVD) prevention in this population. METHODS: Baseline data from the Fukuoka Kidney Disease Registry (FKR) cohort, which included 4476 adult patients with CKD stages G1-G5, were cross-sectionally analyzed to compare the use of recommended drugs for preventing CVD in each age group. RESULTS: Different prescribing patterns were observed according to age for the cardiovascular drug classes. Older patients with CKD were less likely to receive renin-angiotensin system (RAS) inhibitors and were more likely to receive calcium channel blockers. The proportion of anticoagulation prescriptions for patients with CKD and atrial fibrillation decreased in the older age group (≥ 75 years). However, the proportion of antiplatelet therapy in patients with ischemic CVD increased linearly with age, even in the very old group aged ≥ 85 years. These findings suggest a severe cardiovascular burden in patients with CKD. Notably, RAS inhibitor use was avoided in the older group despite a severe cardiovascular burden, such as a high prevalence of CVD history and massive albuminuria ＞300 mg/g creatinine. This finding indicates that an older age independently contributed to the non-use of RAS inhibitors, even after adjusting for other covariates. CONCLUSIONS: This study suggests that age is a potential barrier to the treatment of patients with CKD and highlights the need to establish individualized treatment strategies for cardiovascular protection in this population.

A case of seronegative microscopic polyangiitis following the diagnosis of renal pelvic carcinoma.

The incidence rate of malignancy in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is higher than that in the general population. Malignancy has been indicated to be a risk factor or inducer of AAV. Herein, we report the case of a healthy 84-year-old man with seronegative microscopic polyangiitis (MPA) after the diagnosis of renal pelvic carcinoma. Four weeks before admission, his estimated glomerular filtration rate (eGFR) was 85 ml/min/1.73 m2, and no hematuria or proteinuria was detected. Renal biopsy on admission revealed invasive urothelial carcinoma of the right renal pelvis. On day 15, his eGFR decreased to 30 ml/min/1.73 m2 without any incitement. The renal specimen extracted via right robot-assisted nephroureterectomy indicated the presence of ANCA-associated glomerulonephritis. On day 37, urinary protein/urinary creatinine level of 6.48 g/gCre, serum albumin level of 2.1 mg/dL, and eGFR of 20 ml/min/1.73 m2 indicated the presence of nephrotic syndrome. His blood sputum was analyzed via chest computed tomography, which revealed alveolar hemorrhage. Although his myeloperoxidase-ANCA was negative, he was diagnosed with MPA based on the 2022 American College of Rheumatology/European League Against Rheumatism classification criteria. This is the first case report of  MPA or AAV complicated with renal pelvic carcinoma. The clinical indicators demonstrated that renal pelvic carcinoma preceded the onset of MPA. The spatial proximity of both diseases indicated that renal pelvic carcinoma had some influence on MPA development via the mechanism of inflammatory cytokines or neutrophil extracellular traps. Our report may be useful in elucidating the mechanism of MPA development.

History of fragility fracture is associated with cardiovascular mortality in hemodialysis patients: the Q-Cohort study.

INTRODUCTION: In patients undergoing dialysis, major bone fracture is associated with a high risk of mortality, including death of cardiovascular (CV) origin. In the present study, we aimed to determine whether a history of fragility fracture is a predictor of CV death in patients undergoing hemodialysis with long-term follow-up. MATERIALS AND METHODS: In total, 3499 patients undergoing hemodialysis were analyzed for 10 years. We evaluated the history of fragility fracture in each patient at enrollment. The primary outcome was CV death. A Cox proportional hazard model and a competing risk approach were applied to determine the association between a history of fragility fracture and CV death. RESULTS: A total of 346 patients had a history of fragility fracture at enrollment. During a median follow-up of 8.8 years, 1730 (49.4%) patients died. Among them, 621 patients experienced CV death. Multivariable Cox analyses after adjustment for confounding variables showed that a history of fragility fracture was associated with CV death (hazard ratio, 1.47; 95% confidence interval, 1.16-1.85). In the Fine-Gray regression model, a history of fragility fracture was an independent risk factor for CV death (subdistribution hazard ratio, 1.36; 95% confidence interval, 1.07-1.72). CONCLUSION: In a large cohort of patients undergoing hemodialysis, a history of fragility fracture was an independent predictor of CV death.

Association between glycated albumin and sudden death in patients undergoing hemodialysis.

BACKGROUND: The frequency of sudden death and its risk factors in patients undergoing hemodialysis are unknown. This study was performed to examine the association between glycated albumin (GA) and sudden death in Japanese patients undergoing hemodialysis. METHODS: In total, 260 patients undergoing hemodialysis aged ≥18 years were retrospectively followed for a mean of 4.6 years. The patients' serum GA levels were divided into tertiles, and the patients' sex, age, albumin level, C-reactive protein (CRP) level, and cardiothoracic ratio (CTR) were selected as adjustment factors. A logistic regression model was used to calculate the odds ratio (OR) for the occurrence of sudden death by GA level. RESULTS: Ninety-one patients died during follow-up. Of the 91 deaths, 23 (25.2%) were defined as sudden deaths. Compared with non-sudden death cases, sudden death cases were significantly younger (p = 0.002) and had a higher proportion of men (p = 0.03), a higher proportion of diabetes (p = 0.008), and higher GA levels (p = 0.023). Compared with patients with the lowest GA levels (<15.2%), those with the highest GA levels (≥18.5%) had a sex- and age-adjusted OR for sudden death of 5.40 [95% confidence interval (CI): 1.35-21.85]. After adjusting for the albumin level, CRP level, and CTR in addition to sex and age, the OR for sudden death of patients with the highest GA levels increased to 6.80 (95%CI: 1.64-28.08); the relationship did not change. CONCLUSION: Serum GA levels were significantly associated with sudden death in patients undergoing hemodialysis.

Association of serum magnesium levels with renal prognosis in patients with chronic kidney disease.

BACKGROUND: Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients. METHODS: This is an analysis of the Japan Chronic Kidney Disease Database Ex　(J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7 mg/dl), normal (1.7-2.6 mg/dl), or high (>2.6 mg/dl). The primary outcomes were the composite of an eGFR < 15 ml/min/1.73 m2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression. RESULTS: The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium. CONCLUSION: Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes.

Association between Vascular Calcification and Intraplaque Hemorrhage in Coronary Atherosclerosis from Autopsy: The Hisayama Study.

AIMS: Vascular calcification is observed in advanced atherosclerotic lesions. Vascular calcification is considered to increase the risk of intraplaque hemorrhage and subsequent plaque destabilization; however, there is limited pathohistoological evidence of the association between vascular calcification and intraplaque hemorrhage. The aim of this study was to investigate the association between vascular calcification and intraplaque hemorrhage in the coronary arteries. METHODS: We examined 374 coronary arteries obtained from the autopsy samples of 126 deceased individuals. The vascular calcification levels of each artery were categorized into no calcification and quintiles of calcification area size among the arteries with calcification. Macrophage infiltration and neovascularization were also evaluated. The association of the calcification area, macrophage area, or number of vessels with the presence of intraplaque hemorrhage in the coronary arteries was estimated using a logistic regression analysis. RESULTS: Calcification lesions were observed in 149 coronary arteries. Arteries in the fourth quintile of calcification area size had a significantly greater likelihood of intraplaque hemorrhage than the arteries without calcification, after adjusting for confounders: odds ratio 13.13 (95% confidence interval: 2.97-58.16). After evaluating the influence of macrophage infiltration, the highest odds ratio of intraplaque hemorrhage was associated with the combination of large macrophage area and moderately sized calicification areas. The odds ratio of intraplaque hemorrhage additively increased with the combination of calcification and the number of vessels. CONCLUSIONS: The present findings suggest that vascular calcification is significantly associated with intraplaque hemorrhage. The association between vascular calcification and intraplaque hemorrhage may decrease above a certain size of the calcification area.

Association between Hemoglobin A1c and Renal Arteriolar Sclerosis in Subjects Presenting without any Apparent Kidney Dysfunction.

AIMS: Diabetic kidney disease is a major vascular complication in patients with diabetes mellitus (DM). However, the association between the hemoglobin (Hb)A1c levels, notably the prediabetic levels, and renal pathological changes remains unclear. We investigated the association between the HbA1c levels and renal arteriolar lesions in subjects without any apparent kidney dysfunction using a living kidney donor cohort. METHODS: Between January 2006 and May 2016, 393 living kidney donors underwent a "zero-time" biopsy at Kyushu University Hospital. The patients were divided into four groups (HbA1c levels ＜5.6%, 5.6%-5.7%, 5.8%-6.4%, and ≥ 6.5%, or diagnosed with DM [DM group]). Renal arteriolar hyalinization and wall thickening were assessed using semi-quantitative grading. We then investigated the association between the HbA1c levels and renal pathological changes. RESULTS: 158 (40.2%) patients had arteriolar hyalinization and 148 (37.6%) showed wall thickening. A significant correlation was observed between the HbA1c levels and wall thickening (p for trend ＜0.001). An elevated HbA1c level was significantly associated with wall thickening according to a multivariable logistic analysis in subjects with HbA1c levels of 5.6%-5.7% and 5.8%-6.4%, and the DM group, compared with those with HbA1c levels of ＜5.6% (odds ratio [OR], 1.91; 95% confidence interval [CI]: [1.03-3.54] for 5.6%-5.7%, OR, 1.96; 95% CI: [1.09-3.53] for 5.8%-6.4%, and OR, 2.86; 95% CI: [0.91-9.01] for the DM group), whereas arteriolar hyalinization did not increase within the nondiabetic HbA1c levels. CONCLUSIONS: Elevated high-normal HbA1c levels are considered to be independent risk factors for arteriolar wall thickening. Subclinical renal arteriolar sclerosis may develop in patients with prediabetic HbA1c levels.

Significance of Perivascular Aggregates in Kidney Allografts: Evaluation of 1-Year Protocol Biopsies Using Recent Banff Classification.

BACKGROUND: Perivascular aggregates (PVAs) often occur in kidney allografts; however, their significance needs to be re-evaluated in light of changes in the concept and criteria of allograft rejection. METHODS: We reviewed 1-year protocol biopsies in 258 patients with kidney transplants to identify PVAs and concurrent pathology based on the Banff 2017 classification, including revised criteria for chronic active T-cell mediated rejection (CA-TCMR). We investigated the incidence of PVA, concurrent allograft lesions, diagnosis, and graft survival. No prisoners were used in this study, and no participants were coerced or paid. RESULTS: We identified PVA in 81 biopsies (31.4%). The incidence of previous rejection (32.1% vs 12.4%, P= .0003) and total inflammation (1.3 ± 0.8 vs 0.6 ± 0.8, P < .0001), inflammation (0.7 ± 0.8 vs 0.2 ± 0.5, P < .0001), inflammation in the area of interstitial fibrosis and tubular atrophy (1.3 ± 1.2 vs 0.7 ± 0.9, P < .0001), tubulitis (1.4 ± 1.1 vs 0.6 ± 0.9, P < .0001), and interstitial fibrosis scores (1.2 ± 0.9 vs 0.9 ± 0.9, P= .01) were higher in PVA-positive compared with patients with PVA-negative. Diagnoses in the PVA-positive group revealed no rejection in 49.4%, CA-TCMR in 21.0%, borderline changes in 18.5%, and acute TCMR in 6.2%. CA-TCMR was more frequent in patients with PVA-positive (21.0% vs 4.0%, P < .0001). Graft survival was similar in both groups among all patients, no-rejection, any type of rejection, and CA-TCMR subgroups. CONCLUSIONS: PVAs occur heterogeneously and are associated with previous rejection or concurrent CA-TCMR. The prognostic significance of PVAs in kidney transplantation is inconclusive, and further investigations are needed.

A Single-Center Retrospective Study of Re-Transplantation After Allograft Failure in Kidney Transplant Recipients.

BACKGROUND: This study aimed to examine the outcomes of kidney retransplantation in patients with allograft failure at Kyushu University. METHODS: We reviewed data from 1043 consecutive patients (including 1001 in a first kidney transplantation [KT] group and 42 in a second KT group) who had undergone KT alone at our institution between January 2008 and September 2022. We also studied immunologic risks and outcomes of patients who had undergone preoperative testing for KT at Kyushu University during the same period. RESULTS: No patient received more than 2 transplants. Donor-specific anti-HLA antibody (DSA) had been detected in a greater percentage of patients in the second KT group than in the first (31% vs 11%, respectively; P < .001). There were no significant differences in 5-year death-censored/overall graft survival rates, rates of surgical complications, or incidence of delayed graft function between the groups. During the study period, significantly more candidates for second than first KT were rejected for this procedure because of their high immunologic risk (20% vs 2%, P < 001). Seven of the 42 patients in the second KT group required the removal of the primary graft during the second transplantation. CONCLUSION: There is a higher percentage of patients whose DSA has been detected among patients undergoing retransplantation after allograft failure than among those receiving first KTs, which often leads to remaining on the waiting list in the former group. However, if the immunologic risk is within acceptable limits, the graft survival for retransplantation is not inferior to that of a first KT.

Relationships of Weight Change from 20 Years of Age with the Risks of All-Cause and Cardiovascular Mortality in Patients with Chronic Kidney Disease.

AIMS: Weight changes from a young age are known to be associated with poor life outcomes in the general population. However, little is known about the association between weight change from a young age and life expectancy in patients with chronic kidney disease (CKD). METHODS: Data of 2,806 nondialysis CKD patients who participated in the Fukuoka Kidney Disease Registry (FKR) Study, a multicenter observational study, were analyzed. The primary outcome was all-cause death, whereas the secondary outcome was cardiovascular mortality. The covariate of interest was weight change, defined as the difference between body weight at study enrollment and at 20 years old. Cox proportional-hazards models were used to estimate the risks of mortality for participants with weight changes of ≥ 5 or ＜5 kg compared with those with stable weights. RESULTS: During the 5-year observation period, 243 participants died from all causes and 62 from cardiovascular disease. The risk of all-cause mortality in the weight-loss group was significantly higher than that in the stable-weight group (multivariable-adjusted hazard ratio, 2.11; 95% confidence interval [CI], 1.52-2.93). Conversely, the risk of cardiovascular mortality in the weight-loss group was significantly higher than that in the stable-weight group (multivariable-adjusted hazard ratio, 2.48; 95% CI, 1.32-4.64). However, no significant association was observed between weight gain and the risks of all-cause and cardiovascular mortalities. CONCLUSION: Weight loss from 20 years of age was found to be associated with higher risks of all-cause and cardiovascular mortalities in patients with CKD.