Non-dipping pulse rate and chronic changes of the kidney in patients with chronic kidney disease.

Introduction: An insufficient decrease in nocturnal pulse rate (PR), non-dipping PR, reflects autonomic imbalance and is associated with cardiovascular events and all-cause mortality. We aimed to investigate the clinical and microanatomical structural findings associated with the non-dipping PR status in patients with chronic kidney disease (CKD). Methods: This cross-sectional study included 135 patients who underwent ambulatory blood pressure monitoring and kidney biopsy concurrently at our institution between 2016 and 2019. Non-dipping PR status was defined as (daytime PR-nighttime PR)/daytime PR <0.1. We compared clinical parameters and microstructural changes in the kidney between patients with and without non-dipping PR, including 24 h proteinuria, glomerular volume, and Mayo Clinic/Renal Pathology Society Chronicity Score. Results: The median age was 51 years (interquartile range: 35-63), 54% of which were male, and the median estimated glomerular filtration rate was 53.0 (30.0-75.0) mL/min/1.73 m2. Non-dipping PR status was observed in 39 patients. Patients with non-dipping PR were older and had worse kidney function, higher blood pressure, greater prevalence of dyslipidemia, lower hemoglobin levels, and a larger amount of urinary protein excretion than patients with dipping PR. Patients with non-dipping PR had more severe glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriosclerosis. In the multivariable analysis, the severe chronic changes of the kidney were associated with non-dipping PR status after adjusting for age, sex, and other clinical parameters (odds ratio = 20.8; 95% confidence interval, 2.82-153; P = 0.003). Conclusion: This study is the first to indicate that non-dipping PR is significantly associated with chronic microanatomical changes in the kidneys of patients with CKD.

Long-Term Renal Survival in Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis With Complement C3 Deposition.

INTRODUCTION: Recent studies have revealed the pivotal role of complement activation in the pathogenesis of antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). This study investigated the clinicopathologic and prognostic significance of glomerular C3 deposition in the renal histopathology of patients with ANCA-GN. METHODS: We retrospectively identified 142 patients with ANCA-GN from 6 hospitals in Japan (2004-2020). C3 deposition was defined as C3 staining ≥1+ on a scale of 0 to 2+ using direct immunofluorescence (IF). The primary composite end points included a 30% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), and death. We compared clinicopathologic features and long-term outcomes between patients with and without C3 deposition. RESULTS: C3 deposition was observed in 56 of 142 kidney biopsy samples (39.4%). Patients with C3 deposition had a lower serum C3 level (P = 0.002). During a median follow-up of 2.9 (interquartile range: 0.2-5.7) years, 69 events occurred and the cumulative event-free survival rate at 5 years was significantly lower in the C3-positive group than in the C3-negative group (log-rank: P = 0.002). In multivariable analysis, C3 deposition was significantly associated with the composite end points after adjusting for age, sex, baseline eGFR, serum C3 level, treatment, and the percentage of normal glomerulus, cellular crescents, global sclerosis, and interstitial damage (adjusted hazard ratio [HR] = 2.02, 95% confidence interval: 1.20-3.40, P = 0.008). CONCLUSION: This study revealed that ANCA-GN patients with glomerular C3 deposition on IF had worse renal and overall survival rates.

A case of intravascular large B-cell lymphoma with renal involvement presenting with elevated serum ANCA titers.

We report the first case of intravascular large B-cell lymphoma (IVLBCL) presenting with vasculitis-like symptoms and elevated serum levels of anti-neutrophil cytoplasmic antibody (ANCA) diagnosed by renal biopsy. The patient exhibited low-grade fever, systemic inflammatory reactions, multiple lung lesions, and persistent proteinuria, which were closely correlated with changes in serum titers of proteinase-3- and myeloperoxidase-ANCA. Preemptive therapy with prednisolone alone partially attenuated these symptoms. Renal biopsy did not reveal histopathological findings suggestive of granulomatous or microscopic polyangiitis. Glomerular and peritubular capillaries were diffusely occluded by CD20-positive large atypical mononuclear cells, with focal foot process effacement of podocytes in the glomeruli. Based on the specific immunophenotype of infiltrated atypical cells, the patient was diagnosed with IVLBCL. Chemotherapy regimens for IVLBCL improved clinical symptoms and led to remission of proteinuria. The ANCA titers decreased in parallel with reductions in the serum levels of the soluble interleukin-2 receptor, suggestive of an association between changes in ANCA levels and IVLBCL-related vascular injuries.

Dietary Protein Intake and Single-Nephron Glomerular Filtration Rate.

High protein intake can increase glomerular filtration rate (GFR) in response to excretory overload, which may exacerbate the progression of kidney disease. However, the direct association between glomerular hemodynamic response at the single-nephron level and dietary protein intake has not been fully elucidated in humans. In the present study, we evaluated nutritional indices associated with single-nephron GFR (SNGFR) calculated based on corrected creatinine clearance (SNGFRCr). We retrospectively identified 43 living kidney donors who underwent enhanced computed tomography and kidney biopsy at the time of donation at Jikei University Hospital in Tokyo from 2007 to 2018. Total nephron number was estimated with imaging-derived cortical volume and morphometry-derived glomerular density. SNGFRCr was calculated by dividing the corrected creatinine clearance by the number of non-sclerosed glomeruli (NglomNSG). The mean (± standard deviation) NglomNSG/kidney and SNGFRCr were 685,000 ± 242,000 and 61.0 ± 23.9 nL/min, respectively. SNGFRCr was directly associated with estimated protein intake/ideal body weight (p = 0.005) but not with body mass index, mean arterial pressure, albumin, or sodium intake. These findings indicate that greater protein intake may increase SNGFR and lead to glomerular hyperfiltration.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis during pregnancy.

An 11-week pregnant, 32-year-old Japanese woman who had recovered from infectious mononucleosis visited our center due to fever, anorexia, and bilateral hypochondrial pain. Blood tests revealed leukopenia, thrombocytopenia and elevated ferritin. She was diagnosed with hemophagocytic lymphohistiocytosis (HLH). A high viral load of the Epstein-Barr virus (EBV) was recognized, indicating EBV-HLH. She was treated with a single dose of dexamethasone to protect the fetus. However, the disease was uncontrollable, necessitating etoposide and cyclosporine administration. Remission was obtained with these medications, and she has remained in remission for the 10 months since completion of chemotherapy. Although the occurrence of EBV-HLH during pregnancy is rare, it is possible that a change in cellular immunity associated with the pregnancy may contribute to EBV-HLH development.