Heterogeneous afferent arteriolopathy: a key concept for understanding blood pressure-dependent renal damage.

Hypertension, aging, and other factors are associated with arteriosclerosis and arteriolosclerosis, primary morphological features of nephrosclerosis. Although such pathological changes are not invariably linked with renal decline but are prevalent across chronic kidney disease (CKD), understanding kidney damage progression is more pragmatic than precisely diagnosing nephrosclerosis itself. Hyalinosis and medial thickening of the afferent arteriole, along with intimal thickening of small arteries, can disrupt the autoregulatory system, jeopardizing glomerular perfusion pressure given systemic blood pressure (BP) fluctuations. Consequently, such vascular lesions cause glomerular damage by inducing glomerular hypertension and ischemia at the single nephron level. Thus, the interaction between systemic BP and afferent arteriolopathy markedly influences BP-dependent renal damage progression in nephrosclerosis. Both dilated and narrowed types of afferent arteriolopathy coexist throughout the kidney, with varying proportions among patients. Therefore, optimizing antihypertensive therapy to target either glomerular hypertension or ischemia is imperative. In recent years, clinical trials have indicated that combining renin-angiotensin system inhibitors (RASis) and sodium-glucose transporter 2 inhibitors (SGLT2is) is superior to using RASis alone in slowing renal function decline, despite comparable reductions in albuminuria. The superior efficacy of SGLT2is may arise from their beneficial effects on both glomerular hypertension and renal ischemia. A comprehensive understanding of the interaction between systemic BP and heterogeneous afferent arteriolopathy is pivotal for optimizing therapy and mitigating renal decline in patients with CKD of any etiology. Therefore, in this comprehensive review, we explore the role of afferent arteriolopathy in BP-dependent renal damage.

The Association of Smoking and Hyperuricemia with Renal Arteriolosclerosis in IgA Nephropathy.

The combination effects of smoking (SMK) and hyperuricemia (HU) on renal arteriolosclerosis in patients with IgA nephropathy remain unknown. We examined the cross-sectional association between smoking (current or former) and renal arteriolar hyalinosis and wall thickening with or without HU [uric acid (UA) level ≥ 7 and ≥5 mg/dL in men and women] in 87 patients with IgA nephropathy who underwent renal biopsy. Arteriolar hyalinosis and wall thickening were assessed by the semiquantitative grading of arterioles. The SMK/HU subgroup showed the highest indices for hyalinosis and wall thickening, followed by the non-SMK/HU, SMK/non-HU, and non-SMK/non-HU subgroups. Multiple logistic analysis showed that SMK/HU, but not SMK/non-HU, was significantly associated with an increased risk of higher-grade renal arteriolar wall thickening. However, this did not occur with hyalinosis compared to non-SMK/non-HU. The adjusted odds ratio (95% confidence interval, p value) for SMK/HU was 12.8 (1.36-119, p < 0.05) for wall thickening. An association between SMK and renal arteriolar wall thickening might be prevalent only among patients with HU and in patients with IgA nephropathy. Further prospective studies are needed to determine whether patients with HU and SMK history exhibit rapid eGFR deterioration.

Association of blood pressure and hyperuricemia with proteinuria and reduced renal function in the general population.

This study aimed to investigate the effect of hyperuricemia (HU) on the association of systolic blood pressure (SBP) with the prevalence of proteinuria and low estimated glomerular filtration rate (eGFR) in the general population. This cross-sectional study enrolled 24,728 Japanese individuals (11,137 men and 13,591 women) who underwent health checkups in 2010. The prevalence of proteinuria and low eGFR (< 60 mL/min/1.73 m2) among participants classified according to serum uric acid levels and SBP was compared. HU was defined as serum uric acid levels higher than the 75th percentile in male and female participants (> 7.2 and > 5.4 mg/dL, respectively). The odds ratio (OR) for proteinuria increased with elevated SBP. This trend was significantly evident in participants with HU. Moreover, there was an interactive effect of SBP and HU on the prevalence of proteinuria in the male (Pfor interaction = 0.04) and female (Pfor interaction = 0.04) participants. Next, we evaluated the OR for low eGFR (< 60 mL/min/1.73 m2) with and without proteinuria based on the presence of HU. The multivariate analysis revealed that the OR for low eGFR with proteinuria increased with elevated SBP, but that for low eGFR without proteinuria decreased. These trends of OR tended to be prevalent among those with HU. The association between SBP and the prevalence of proteinuria was more pronounced in participants with HU. However, the association between SBP and decreased renal function with and without proteinuria might be different regardless of HU.

Acquired factor V inhibitor with erythema and eosinophilia in a patient with end-stage renal disease.

Autoimmune factor V deficiency (AiFVD) is a rare bleeding disorder caused by factor V inhibitors. In this report, we present the case of an 89-year-old man who developed bleeding tendency during surgery to create arteriovenous fistula for hemodialysis. The bleeding tendency developed with prolongation of activated partial thromboplastin and prothrombin time, following drug-induced eruption and eosinophilia. Significant reduction in coagulation factor activity and inhibitory pattern in cross-mixing tests suggested the presence of inhibitors to coagulation factors. Subsequently, we detected a factor V inhibitor and anti-factor V autoantibodies was confirmed using enzyme-linked immunosorbent assay with purified human plasma factor V. Thus, the patient was 'definitely diagnosed' with AiFVD in accordance with the diagnostic criteria enacted by the Japanese Ministry of Health, Labor, and Welfare. The bleeding tendency improved after initiating oral prednisolone 50 mg (1 mg/kg) followed by normalization of activated partial thromboplastin time and prothrombin time at the 34th day. After improving the coagulation system prolongation, the inhibitor and autoantibodies has been eradicated. Since it is suggested that drug-induced immune response can cause AiFVD, AiFVD should be considered in patients who undergo hemodialysis and develop failure of hemostasis and drug-induced eruption.

Association of urinary angiotensinogen with renal arteriolar remodeling in chronic kidney disease.

OBJECTIVE: Renin-angiotensin system (RAS) might be associated with arteriolar remodeling. The present study aimed to explore the hitherto unknown relationship between renal RAS and renal arteriolar remodeling and to elucidate whether altered renal RAS subsequently affects renal function in patients with chronic kidney disease (CKD). METHODS: In this retrospective study, patients with various CKDs not using RAS inhibitors who underwent renal biopsy were included in cross-sectional and longitudinal analyses. Urinary angiotensinogen (UAGT) levels and wall/lumen ratio (WLR) were determined to evaluate renal RAS and renal arteriolar remodeling, respectively. The association between ln(UAGT) and ln(WLR) was cross-sectionally examined using a liner regression model. Furthermore, the association of ln(UAGT) with subsequent changes in estimated glomerular filtration rate (eGFR) per year were longitudinally examined in the largest subgroup of patients who were diagnosed with IgA nephropathy. RESULTS: In the overall cohort (n = 54), the median age, blood pressures, eGFR, and WLR were 37 years, 120/73 mmHg, 85 ml/min per 1.73 m2, and 0.93, respectively. Ln(UAGT) was significantly and positively associated with ln(WLR) even after adjusting for classical and nonclassical clinical renal risk factors. In patients with IgA nephropathy, higher ln(UAGT) was associated with higher ln(WLR). Ln(UAGT) also tended to be associated with a greater decline in eGFR per year over a median period of 8.7 years, even after adjusting for potential confounding factors. CONCLUSION: In patients with CKD, renal RAS might be associated with renal arteriolar remodeling and future decline in eGFR, independent of potential risk factors.

Incidental detection of Corynebacterium jeikeium endocarditis via regular blood examination in an afebrile hemodialysis patient.

Herein, we describe a rare case of Corynebacterium jeikeium endocarditis that silently progressed in a 65-year-old man undergoing hemodialysis. Because routine monthly blood examination revealed high C-reactive protein levels, blood cultures were collected, although he had no symptom and was afebrile. After 2 days, a Gram-positive rod was detected in one set of the blood culture. Furthermore, transthoracic echocardiography revealed new aortic regurgitation (AR) and vegetations, and, therefore, infective endocarditis was suspected. Transesophageal echocardiography showed vegetations with a maximum diameter of 8 mm on his aortic valve, with some valve destruction. C. jeikeium was identified in three sets of blood cultures. Administration of daptomycin was started because he had vancomycin allergy. Judging from the high risk of embolization due to vegetations, emergency aortic valve replacement was performed on the second day. C. jeikeium was detected in a resected cardiac valve specimen and blood. This case emphasizes that physicians should always consider the possibility of infective endocarditis even in hemodialysis patients without any symptoms.