Epigenetic roles in clonal hematopoiesis and aging kidney-related chronic kidney disease.

Accumulation of somatic hematopoietic stem cell mutations with aging has been revealed by the recent genome-wide analysis. Clonal expansion, known as clonal hematopoiesis of indeterminate potential (CHIP), is a premalignant condition of hematological cancers. It is defined as the absence of definitive morphological evidence of a hematological neoplasm and occurrence of ≥2% of mutant allele fraction in the peripheral blood. In CHIP, the most frequently mutated genes are epigenetic regulators such as DNMT3A, TET2, and ASXL1. CHIP induces inflammation. CHIP is shown to be associated with not only hematological malignancy but also non-malignant disorders such as atherosclerosis, cardiovascular diseases and chronic liver disease. In addition, recent several large clinical trials have shown that CHIP is also the risk factor for developing chronic kidney disease (CKD). In this review article, we proposed novel findings about CHIP and CHIP related kidney disease based on the recent basic and clinical research. The possible mechanism of the kidney injury in CHIP is supposed to be due to the clonal expansion in both myeloid and lymphoid cell lines. In myeloid cell lines, the mutated macrophages increase the inflammatory cytokine level and induce chronic inflammation. It leads to epigenetic downregulation of kidney and macrophage klotho level. In lymphoid cell lines, CHIP might be related to monoclonal gammopathy of renal significance (MGRS). It describes any B cell or plasma cell clonal disorder that does not fulfill the criteria for cancer yet produces a nephrotoxic monoclonal immunoglobulin that leads to kidney injury or disease. MGRS causes M-protein related nephropathy frequently observed among aged CKD patients. It is important to consider the CHIP-related complications such as hematological malignancy, cardiovascular diseases and metabolic disorders in managing the elderly CKD patients. There are no established therapies for CHIP and CHIP-related CKD yet. However, recent studies have supported the development of effective CHIP therapies, such as blocking the expansion of aberrant HSCs and inhibiting chronic inflammation. In addition, drugs targeting the epigenetic regulation of Klotho in the kidney and macrophages might be therapeutic targets of CHIP in the kidney.

A case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) that responded favorably to steroid therapy.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) generally has a poor prognosis and the consensus is that it needs to be treated with clone-directed therapy. However, the prognosis of PGNMID is heterogenous and some cases have been successfully treated using other therapeutic strategies. We herein report a case of PGNMID that responded favorably to steroids without clone-directed therapy. An 18-year-old woman was referred to a nephrologist with proteinuria detected in an annual health check-up. Over a 3-year period, the concentration of creatinine (Cr) increased from 0.76 to 1.00 mg/dL and proteinuria from 0.35 to 1.9 g/g Cr. Monoclonal gammopathies were not detected in her serum or urine. Based on the findings of kidney biopsy at the age of 21 years, the patient was diagnosed with proliferative glomerulonephritis with monoclonal IgG1-kappa deposits. The histological feature was mesangial proliferative glomerulonephritis with advanced glomerulosclerosis, which is a rare presentation of PGNMID. Intravenous methylprednisolone pulse therapy was initiated, followed by oral prednisolone at a dose of 30 mg daily. One year later, a second kidney biopsy revealed a significant decrease in mesangial deposits of IgG1-kappa. Prednisolone was gradually tapered and discontinued 2 years after the first kidney biopsy. At the time of prednisolone withdrawal, urinalysis showed proteinuria of 0.2 g/g Cr without hematuria. Kidney function remained stable throughout the treatment period.

Incidence and risk factors of contrast-induced nephropathy after transcatheter arterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is widely used for unresectable hepatocellular carcinoma (HCC). The purpose of this study was to investigate incidence and risk factors of contrast-induced nephropathy (CIN) after TACE in patients with HCC. METHODS: In this single-center retrospective study, we examined 461 consecutive TACE sessions in 260 patients between January 2003 and October 2015. CIN was defined as an increase in serum creatinine levels by ≥ 0.5 mg/dl or ≥ 25% from baseline within 72 h after TACE. We calculated incidence rate of CIN and tried to identify its risk factors by logistic regression analysis. RESULTS: Twenty-one cases of CIN (5%) were observed in 461 TACE sessions. One patient required subsequent hemodialysis transiently. In univariate analysis, tumor size > 5 cm [odds ratio (OR) 5.76, 95% confidence interval (CI) 2.34-14.14, p < 0.001], chronic kidney disease (OR 2.54, 95% CI 1.05-6.14, p = 0.04), serum hemoglobin level [OR 0.79 (per 1 g/dl increase), 95% CI 0.64-0.98, p = 0.03] and serum albumin level [OR 0.44 (per 1 g/dl increase), 95% CI 0.19-1.02, p = 0.05] were associated with the development of CIN. Stepwise logistic regression methods showed that tumor size > 5 cm (OR 7.81, 95% CI 2.99-20.46, p < 0.001) and serum albumin [OR 0.29 (per 1 g/dl increase), 95% CI 0.11-0.75, p = 0.01] were risk factors of CIN. CONCLUSIONS: In this study, HCC tumor size and lower serum albumin level were independent predictors of CIN after TACE.