Jun Zou

Background: Autoimmune hemolytic anemia (AIHA) is an uncommon acquired disorder that can lead to life-threatening intravascular hemolysis and acute kidney injury (AKI). Hemoglobin cast nephropathy is a rare but severe complication of massive hemolysis, often underrecognized in clinical practice. Case presentations: We describe a 57-year-old female with no prior chronic kidney disease who presented with nausea, vomiting, oliguria, edema, and rapidly progressive renal dysfunction after a presumed preceding infectious-like episode. Laboratory investigations revealed severe anemia, elevated hemolytic markers, and a positive direct antiglobulin test (DAT) for complement C3 (C3d) and negative for IgG. Renal biopsy demonstrated acute tubular injury with hemoglobin casts confirmed by immunostaining, consistent with hemoglobin cast nephropathy. The patient was treated with intermittent renal replacement therapy, intravenous methylprednisolone, and supportive care. Renal function and hemoglobin levels gradually normalized, and she remained well without relapse over 11.5 months of follow-up. Conclusion: This case highlights that when acute kidney injury and hemolytic anemia occur concurrently, hemoglobin cast nephropathy should be strongly suspected. Renal biopsy is valuable when the diagnosis is uncertain. Early immunosuppressive therapy, renal replacement therapy, and supportive care can lead to favorable outcomes.

Membranous nephropathy is the most common glomerular disease related to malignancy. However, it is difficult to distinguish between true malignancy-related membranous nephropathy and idiopathic membranous nephropathy coincident with cancer. It has been reported that phospholipase A2 receptor (PLA2R) is the first autoantigen involved in idiopathic membranous nephropathy and thrombospondin type-1 domain-containing 7A (THSD7A) may have a close relationship with malignancy-related membranous nephropathy. Therefore, the aim of this study was to compare the clinicopathological characteristics between membranous nephropathy patients with cancer and idiopathic membranous nephropathy patients without cancer to better detect malignancy-related membranous nephropathy, including glomerular PLA2R and THSD7A depositions and their circulating antibodies, together with glomerular IgG4 deposition. Twelve membranous nephropathy patients with cancer and 257 idiopathic membranous nephropathy patients without cancer were included in this study and had been followed up for more than 1 year. The glomerular expression of PLA2R, THSD7A, and IgG4 was analyzed by immunohistochemistry. Circulating anti-PLA2R and anti-THSD7A antibodies were assessed by enzyme-linked immunosorbent assay and indirect immunofluorescence testing, respectively. Membranous nephropathy patients with cancer were significantly older and had higher serum creatinine and a lower estimated glomerular filtration rate than idiopathic membranous nephropathy patients (PP<0.01). The absence of glomerular PLA2R deposition and negative circulating anti-PLA2R antibodies, along with negative glomerular IgG4 staining, may be useful clues to more accurately screen underlying malignancies in membranous nephropathy patients.

BACKGROUND:M-type phospholipase A2 receptor (PLA2R) was identified as the major target antigen in idiopathic membranous nephropathy (IMN). Another target antigen, namely thrombospondin type-1 domain-containing 7A (THSD7A), was recently detected in ap...

NOD‐like receptor family caspase recruitment domain family domain containing 5 (NLRC5) has important roles in inflammation and innate immunity. NLRC5 was highly expressed in kidney from streptozotocin‐induced diabetic mice, db/db mice and patients with diabetes. Based on that evidence, the present study was designed to explore the roles of NLRC5 in the progression of diabetic nephropathy (DN). We examined kidney injury, including inflammation and fibrosis in Nlrc5 gene knockout ( Nlrc5 ^−/− ) and wild‐type (WT) diabetic mice. We found that Nlrc5 ^−/− mice developed less‐severe diabetic kidney injury compared with WT mice, exhibiting lower albuminuria, less fibronectin and collagen IV expression, and reduced macrophage infiltration but greater levels of podocin and nephrin in the diabetic kidney. The underlying mechanisms were further investigated in vitro with peritoneal macrophages and mesangial cells treated with high glucose. Reduced proinflammatory effect was observed in peritoneal macrophages from Nlrc5 ^−/− mice, associated with NF‐κB pathway suppression. Knocking down of NLRC5 in mesangial cells in high‐glucose conditions was also associated with reduced NF‐κB and TGF‐β/Smad signaling. Taken together, NLRC5 promotes inflammation and fibrosis during DN progression partly through the effects on NF‐κB and TGF‐β/Smad pathways. NLRC5 may, therefore, be a promising therapeutic target for DN treatment.—Luan, P., Zhuang, J., Zou, J., Li, H., Shuai, P., Xu, X., Zhao, Y., Kou, W., Ji, S., Peng, A., Xu, Y., Su, Q., Jian, W., Peng, W. NLRC5 deficiency ameliorates diabetic nephropathy through alleviating inflammation. FASEB J. 32, 1070–1084 (2018). www.fasebj.org

There is abundant evidence that sodium intake is related to blood pressure. However, the relationship varies between individuals and is probably determined by renal sodium handling. We investigated clinic and ambulatory blood pressure in relation to interactions between sodium dietary intake and renal handling, as assessed by 24-hour urinary sodium excretion and endogenous lithium clearance, respectively. We calculated fractional excretion of lithium and fractional distal reabsorption rate of sodium, as markers of proximal and distal sodium handling, respectively. The 766 subjects included 379 men and 478 ambulatory hypertensive patients. They were never treated (n=697) or did not take antihypertensive medication for ≥2 weeks (n=69). In adjusted analyses, none of the associations of urinary sodium excretion, fractional excretion of lithium, and fractional distal reabsorption rate of sodium with clinic or ambulatory blood pressure were statistically significant ( P ≥0.09). However, there was significant ( P =0.01) interaction between urinary sodium excretion and fractional excretion of lithium in relation to nighttime diastolic blood pressure. In tertile 3 but not tertiles 1 and 2 of fractional excretion of lithium, nighttime diastolic pressure was positively associated with urinary sodium excretion ( P =0.03). However, nighttime diastolic pressure was higher in tertile 1 than tertile 3 of fractional excretion of lithium (+2.0 mm Hg; P =0.01), especially in the bottom tertile of urinary sodium excretion (+4.9 mm Hg; P <0.001). Similar trends were observed for nighttime systolic pressure and clinic and 24-hour diastolic pressure. In conclusion, sodium dietary intake and proximal tubular handling interact to be associated with blood pressure.