2018年 · 第34卷第08期

Hyperphosphatemia is a major complication of patients with chronic kidney disease (CKD). The prevalence of hyperphosphatemia (blood phosphorus>1.78 mmol/L) in CKD patients in China is as high as 71.6%^[1]。 Hyperphosphatemia can lead to secondary hyperparathyroidism, ectopic calcification, cardiovascular disease and other complications, and is an independent risk factor for death in CKD patients^[2,3]。 Establishing a stable mouse model of hyperphosphatemia is of great significance to study the occurrence, development, pathogenic mechanism and treatment of hyperphosphatemia. In this study, the animal model of CKD was prepared with traditional 0.2% adenine combined with high phosphorus diet, so as to construct a more stable and reliable mouse model of CKD hyperphosphatemia.

A 69-year-old male was first admitted to the hospital in April 2011 due to "increased blood pressure, edema with abnormal urine test, and increased creatinine for 3 months". Since January 2011, the patient developed edema of both lower limbs without trigger and no decrease in urine volume. The urine protein was 3+, occult blood was 3+, serum creatinine (Scr) was 132 μ mol/L, albumin (Alb) was 32.9 g/L, and blood pressure was 190/100 mmHg. During the course of the disease, there was no macroscopic hematuria, irregular fever, rash, joint pain, abdominal pain, melena, alopecia, oral ulcer, etc. Blood pressure was 152/96 mmHg, urine protein was 4.64 g/24 h, urine sediment red blood cells were 11 million/ml, and polymorphism was found. Hemoglobin (Hb) 120 g/L, Alb 27.9 g/L, globulin (Glo) 21.7 g/L, Scr 108.7 μ mol/L, negative for infectious diseases, anti-nuclear antibody (ANA), anti-dsDNA antibody negative, complement C3, C4, rheumatoid factor (RF), anti-hemolytic streptococcus "O" (ASO) normal. Renal biopsy light microscope showed "a large number of PAS-positive embolus and complex erythrophils in the loop cavity of membranoproliferative glomerulonephritis", Congo red (-), and immunofluorescence showed "IgG3 and κ in the mesangial area, vascular loop and loop cavity contents showed segmental distribution, IgA, IgM, C1q and C3 were all negative", seeFigure 1。 The electron microscope results were not available, and the initial pathological diagnosis was "proliferative glomerulonephritis with monoclonal IgG deposition (PGNMID)". cryoglobulinemic glomerulonephritis (CGN) should be excluded, and the presence of hematological tumors should be determined. Blood cryoglobulin, immunofixation electrophoresis and hematuria free light chain were examined, bone marrow puncture was performed, and tripterygium wilfordii 60 mg/d and antihypertensive therapy were temporarily given. The patient's blood free light chain ratio was normal, the urine free light chain ratio was 2.41 (reference value 2), and the bone marrow cytology examination showed no abnormalities. The patient was discharged first without completing the blood cryoglobulin and immune fixation electrophoresis examinations, and was ordered to be further examined during follow-up.

A 32-year-old male was admitted to the hospital in December 2017 due to "regular hemodialysis for more than 7 years and loss of function (failure) of arteriovenous fistula for two weeks". In January 2009, the patient was diagnosed with double kidney stones with hydrops due to pain in both kidney areas. He was subjected to extracorporeal shock wave lithotripsy (ESWL) and kidney stone lithotomy successively. In May 2010, due to dizziness and fatigue, the Scr was found to be 2000 μ mol/L, and hemodialysis treatment was started. In March 2011, he underwent allogeneic kidney transplantation in our hospital. The Scr decreased to 114 μ mol/L within 7 days after operation, and the Scr began to increase on the 9th day after operation. Pathological examination of the transplanted kidney showed acute tubular necrosis. After adjusting the immunosuppressant regimen, Scr still increased progressively, and the transplanted kidney biopsy was performed again 48 days after operation. The pathological results showed: focal segmental glomerulosclerosis; Acute tubular necrosis. The dose of prednisone and immunosuppressant regimen continued to be adjusted, but Scr continued to increase progressively. Three months after surgery, the transplanted renal artery was embolized, immunosuppressant was stopped, and regular hemodialysis was performed again. Multiple examinations during the course of the disease showed hypoalbuminemia, three-line reduction, and splenomegaly (191 mm ×65 mm), and the symptomatic treatment effect was not good. Bone marrow cytology examination 2 years ago showed the possibility of metastatic tumor, and bone marrow biopsy showed a large number of osteoclast-like multinucleated cells, but no further diagnosis was obtained. Recently, I gradually developed pain in the joints of my limbs and limited movement. Two weeks before admission, I came to our hospital for treatment due to poor internal fistula function, which could not meet the needs of dialysis. Family history: The patient's parents were close relatives, both parents were in good health, and there was no special medical history.

A 59-year-old male was admitted to the hospital on 27-Nov-2015 due to elevated Scr for 14 d after mistakenly taking antifreeze. The patient accidentally ingested 150 ml of antifreeze 14 days before admission, developed vomiting and frequent urination 2 hours later, and became unconscious 4 hours later. He went to the First Hospital of Jilin University 15 h later. On admission, the patient had an elevated Scr, arterial blood gas analysis showed an elevated anion gap (AG), and metabolic acidosis. SeeTable 1。 Urinary occult blood (3+), urine protein (3+). The diagnosis was "acute kidney injury, metabolic acidosis". Continuous venous-venous hemofiltration (CVVH) was performed immediately. After 48 hours, the patient regained consciousness, but developed anuria symptoms. After 72 hours, the Scr decreased to 146.8 μ mol/L. After 3 times/week of hemodialysis (HD) treatment, the Scr level was maintained at 505.5~668.3 μ mol/L. SeeFigure 1。 On November 27th, the patient was transferred to our hospital for treatment. Physical examination: blood pressure 150/95 mmHg, no facial and extremity edema. Laboratory test: Blood WBC 7.9×10⁹/L, urine protein (2+), urine occult blood (3+), urine specific gravity 1.010, Scr 623.0 μ mol/L. The kidney color ultrasound showed no abnormalities. Renal biopsy was performed on the day of admission, and the results of renal pathological examination showed that immunofluorescence was all negative; Under light microscope, it showed typical acute tubular necrosis (ATN) changes; Calcium oxalate monohydrate (COM) crystals were deposited in the proximal tubules under polarized optical microscope. No obvious pathological changes were observed in the kidney arterioles. Pathological diagnosis: ATN due to oxalate deposition. SeeFigure 2。 The patient's urine output gradually increased from 3 to 6 December (maximum urine volume reached 4000 ml/24 h). However, due to azotemia, the patient continued to receive HD treatment 3 times/week, discontinued HD on 10 December, and renal function completely returned to normal after 6 months.

autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Very few patients present with nephrotic syndrome (NS). Its treatment and prognosis depend on the pathological type of NS. Due to the destruction of kidney structure in ADPKD, the risk of renal puncture is high, and it is difficult to obtain ideal pathological tissue. Therefore, other diagnostic methods need to be found to clarify the pathological type of kidney in such patients. In this case, the patient's kidney pathological type was identified as idiopathic membranous nephropathy (IMN) by detecting serum anti-phospholipase A2 receptor (PLA2R) antibody. After immunosuppressant treatment, the condition reached complete remission, which is reported as follows.

Renin-angiotensin-aldosterone system (RAAS) is mainly composed of renin, angiotensin Ⅰ (AngⅠ), angiotensin Ⅱ (AngⅡ), angiotensin converting enzyme, aldosterone, etc. It is an important system for regulating water and salt metabolism, and plays an important role in the normal development of cardiovascular system, cardiovascular homeostasis, maintenance of electrolyte and fluid balance, and regulation of blood pressure. Aldosterone is the end product of RAAS and belongs to steroid hormones. It mainly acts on the kidney and is an important hormone for maintaining extracellular fluid capacity and electrolyte balance^[1]。 Current studies have confirmed that excessive RAAS activation will increase the risk of cardiovascular disease, and inhibiting or blocking RAAS can alleviate the occurrence of cardiovascular events^[2]。

Nephrotic syndrome (NS) is a common nephrological condition characterized by massive proteinuria, severe hypoalbuminemia, edema and hyperlipidemia. Proteinuria is mainly caused by the destruction of glomerular filtration membrane. The filtration membrane is composed of three layers: endothelial cells, basement membrane and podocytes. The diameter of micropores on the surface of glomerular endothelial cells is 60~100 nm, which is not enough to block albumin (4 nm ×4 nm ×8 nm) and macromolecular substances. Therefore, the long-term research on glomerular filtration barrier mainly focuses on podocytes and basement membrane. However, in recent years, many studies have found that on the surface of endothelial cells and podocyte, there is a layer of 200~400 nm thick polysaccharide-protein complex, called glycoprotein E (GE), which is also an effective component of the filtration membrane, and it is of great significance to maintain the functional integrity of the filtration membrane^[1,2,3]。 In this paper, the role of glycocalyx in the occurrence of NS proteinuria was reviewed, and the feasibility of using glycocalyx as a target to treat NS was discussed, so as to provide theoretical basis for finding new therapeutic targets and drugs for clinical treatment of NS proteinuria.