Autosomal dominant tubulointerstitial kidney disease with a novel heterozygous missense mutation in the uromodulin gene: A case report.

BACKGROUND: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a progressive chronic disease that is inherited in an autosomal dominant fashion. Symptoms include hyperuricemia, gout, interstitial nephritis, renal cysts, and progressive renal damage that can lead to end-stage renal disease. Mutations in the uromodulin gene (UMOD) characterize the ADTKD-UMOD clinical subtype of this disease. To date, > 100 UMOD mutations have been identified. Early diagnosis of ADTKD-UMOD is important to treat the disease, slow down disease progression, and facilitate the identification of potentially affected family members. CASE SUMMARY: We report a 40-year-old man harboring a novel heterozygous missense mutation in UMOD (c.554G>T; p. Arg185Leu). The patient had hyperuricemia, gout, and chronic kidney disease. The same mutation was detected in his daughter, aunt and cousin. CONCLUSION: A single nucleotide substitution in exon 3 of UMOD was responsible for the heterozygous missense mutation (c.554G>T, p.Arg185Leu).

Abdominal hemorrhage after peritoneal dialysis catheter insertion: A rare cause of luteal rupture: A case report.

BACKGROUND: Abdominal hemorrhage is a complication of peritoneal dialysis catheter (PDC) insertion that cannot be neglected, and its causes are mainly related to surgical injury. This article reports a case of massive abdominal hemorrhage that was caused by a rare rupture of corpus luteum shortly after PDC during the initiation of peritoneal dialysis (PD) insertion. CASE SUMMARY: A 37-year-old woman was surgically placed a Tenckhoff catheter because of end-stage renal disease. On the third postoperative day, the color of the abdominal drainage fluid was pink, and deepened gradually. It turned pale after initiating conservative treatment. On the tenth postoperative day, the color of the abdominal drainage fluid suddenly turned dark red, and the color progressively deepened. The patient's hemoglobin dropped from 88 g/L to 57 g/L. Abdominal computed tomography (CT) indicated abdominal effusion and a high-density shadow in the abdominal cavity. The surgeon performed a laparotomy and found that the corpus luteum had ruptured on the right side and a left ovarian blood body had formed. The gynecologist repaired the ovary and performed a bilateral oophoroplasty. After the operation, the patient stopped bleeding and hemodialysis was temporarily stopped. PD was resumed after half a month. The patient's condition improved, and she was discharged 14 d after the laparotomy. CONCLUSION: If abdominal hemorrhage occurs in women of childbearing age after PDC insertion, luteal rupture should be considered as the cause.

Roxadustat as treatment for a blood transfusion-dependent maintenance hemodialysis patient: A case report and review of literature.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) have revolutionized the therapeutic strategy for anemia in chronic kidney disease. However, some cases are resistant or hyporesponsive to ESAs. Roxadustat is an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Here, we describe a hemodialysis patient with refractory anemia who did not respond to traditional treatments and depended on blood transfusion for more than 1 year. After applying Roxadustat, the patient's anemia improved significantly. CASE SUMMARY: A 44-year-old man was diagnosed with uremia accompanied by severe anemia with a hemoglobin (Hb) level ranging from 30-40 g/L. His anemia did not improve after sufficient dialysis or high doses of active ESAs; other causes of anemia were excluded. The patient required approximately 600-1000 mL of red blood cell suspension every 15-30 d for more than 1 year. After accepting Roxadustat therapy, the patient's anemia symptoms improved significantly; his Hb level gradually increased to 50 g/L, and no further blood transfusions were administered. His Hb level reached 69 g/L by the 34th week. Although a Hb level of 60-70 g/L cannot be considered satisfactory, he no longer required blood transfusions and his quality of life was substantially improved. Roxadustat showed good efficacy and safety in this case. CONCLUSION: Roxadustat represents an innovative and effective agent for the clinical treatment of renal anemia caused by multiple complex factors.

[Expression of BMP2/Smad1/Runx2 Signal Pathway in Renal Artery of Rat with Vascular Calcification].

OBJECTIVE: To investigate the activation and its role of bone morphogenetic protein 2 (BMP2)/Smad1/Runt-related transcription factor 2 (Runx2) signal pathway in renal artery of rat models with vascular calcification. METHODS: Twenty four male SD rats were randomly divided into control group and calcification group. Rat vascular calcification model was constructed by administration of vitamin D3 plus nicotine. Vascular calcification was confirmed by Von Kossa staining and calcium content was detected by calcium assay. Real time-PCR was applied to detect the expression of BMP2, Smad1, Runx2 mRNA, and immunohistochemistry was used to measure the protein levels of BMP2, Smad1, Runx2, α-smooth muscle actin (α-SMA). RESULTS: Von Kossa staining showed a large number of black granules deposited in renal artery. Calcium content in calcification group was significantly higher than that in normal group. Compared with the control group, the expressions of BMP2, Smad1 and Runx2 mRNA in renal artery were increased in calcification group. The protein levels of BMP2, Smad1 and Runx2 were higher while the expression of α-SMA was lower in calcification group than those in control group. The correlation analysis was found a positivie correlation between the calcium content and BMP2 mRNA (r = 0.655, P < 0.05), Smad1 mRNA (r = 0.735, P < 0.05), Runx2 mRNA (r = 0.734, P < 0.05). CONCLUSION: The expression of BMP2/Smad1/Runx2 signal pathway was strongly correlated with the severity of vascular calcification, which may be involved in the occurrence and development of vascular calcification.

[Influence of angiotensin-(1-7) on cell activation in rat renal interstitial fibroblasts induced by aldosterone].

AIM: To explore the influence of angiotensin-(1-7) [Ang-(1-7)] on cell activation and extracellular matrix secretion in rat renal interstitial fibroblasts (NRK-49F) induced by aldosterone (ALD). METHODS: The NRK-49F cells were cultured in vitro, and then were divided into control group, ALD group, Ang-(1-7) group, and ALD+Ang-(1-7) group. When the cells were cultured for 48 h, the expression of α-smooth muscle actin (α-SMA) (a sign of cell activation) was detected by immunocytochemistry; the level of collagen type I (Col I ) in the cultured supernatant was measured by enzyme-linked immunosorbent assay (ELISA). When the cells were cultured for 30 min, the expressions of phosphorylated and total ERK1/2 (pERK1/2, tERK1/2) in the cell lysate were detected by Western blotting. RESULTS: Compared with control group, the expressions of α-SMA, Col I and the Phos/Total ERK1/2 ratio in ALD group and ALD+Ang-(1-7) group increased significantly (P<0.05). Compared with ALD group, the expressions of α-SMA, Col I and the Phos/Total ERK1/2 ratio in ALD+Ang-(1-7) group decreased significantly (P<0.05). CONCLUSION: Ang-(1-7) can inhibit ALD-induced cell activation and decrease the secretion of Col I in rat renal interstitial fibroblasts. Inhibition of ERK1/2 pathway may play an important role in this process.

[Relation between bone matrix proteins and monocyte chemoattractant protein-1 in renal small artery in diabetic nephropathy rats].

OBJECTIVE: To observe the expressions of bone matrix proteins and monocyte chemoattractant protein-1 ((MCP-1) in the renal arteriole of diabetic nephropathy (DN) rats and analyze their correlations and roles in diabetic nephropathy. METHODS: Adult Sprague-Dawley male rats were used to establish the animal model of diabetic nephropathy induced by peritoneal injection of 55 mg/kg of streptozocin. Calcium deposit around the renal arteriole was observed by alizarin red staining. The protein and mRNA levels of core-bind factor alpha 1 (cbfalpha1), bone morphogenetic protein 2 (BMP-2) and matrix Gla protein (MGP) in renal arteriole of DN rats were detected by immunohistochemistry, in-situ hybridization and real-time PCR. The biochemical indices were detected by routine test. RESULTS: 1. Blood glucose and Urine protein of 24 h were significantly increased in the renal arteriole of DN rats versus the control rats (P < 0.05), serum creatinine (SCr) and phosphorus were significantly increased from 12 weeks. 2. Little deposit of calcium salt was observed in the renal arteriole of DN rats at the 4th week and a large amount of deposit was observed at 24th week, but no calcium deposit was observed in control rats. 3. Cbfalpha1 and BMP-2 expressions were significantly increased in the renal arteriole of DN rats from 4 to 24 weeks vs. the control rats. MGP mRNA expression in the renal arteriole of DN rats was significantly decreased from 4 to 24 weeks. MCP-1 expression was obviously upregulated in the renal arteriole of DN rats at 24th week versus that at 4th and 12th week. No MCP-1 expression was observed in the renal arterioles of control rats. MCP-1 were positively correlated with the expression of cbfalpha1 and BMP-2. CONCLUSION: Bone matrix proteins has already expressed in renal arteriole before the formation of vascular calcification. MCP-1 can affect the expression of cbfalpha1, BMP-2; cbfalpha1, BMP-2, MGP and MCP-1 may be involved in the formation of vascular lesions of DN.

[Effects of atorvastatin on expression of peroxisome proliferation activated receptor gamma in unilateral ureteral obstruction in rats].

OBJECTIVE: To observe the expression of peroxisome proliferation activated receptor gamma (PPAR gamma) at different periods in renal interstitium and to study the effect of atorvastatin on the protein expression of PPAR gamma in unilateral ureteral obstruction (UUO) in a rat model. METHODS: Forty-five female Sprague-Dawley (SD) rats were divided into three groups: the sham operation group, the model group and the atorvastatin group. The latter two groups underwent UUO and then received vehicle only or atorvastatin (10 mg.kg(-1).d(-1)) by daily gastric gavage, from three days before the UUO operation to the day of sacrifice . The sham operation rats received vehicle. Five rats of each group were sacrificed respectively at 5, 10 and 15 days after surgery. Histological changes in renal tissue were observed by hematoxylin and eosin (HE) and Masson stain. Immunohistochemistry for PPAR gamma was performed in renal interstitium at each time point. RESULTS: Interstitial expansion and fibrosis in ureter obstructed kidney was prominent in the model group. Atorvastatin seemed to have ameliorated interstitial expansion and fibrosis in atorvastatin group. Detectable basic PPAR gamma expression was observed in renal inner medulla of rats in sham operation group, and it was mainly concentrated in collecting tubules. In UUO rats, PPAR gamma expression was found increased and extended to renal tubular epithelial cells. Increased PPAR gamma expression was found on the 5th day after UUO, and significant PPAR gamma expression was found on the 10 th day after UUO. The increased PPAR gamma expression was found to be downregulated on the 15 th day after UUO, but still significantly increased compared with that of the model group at the same time point (all P<0.01). Atorvastatin could significantly increase the expression of PPAR gamma as compared with the model group at each time point (all P<0.01). CONCLUSION: PPAR gamma expression was found increased, and it appeared in renal tubular epithelial cells in UUO rats, Atorvastatin may play a protective role in the kidney by activating PPAR gamma, thus alleviating renal interstitial fibrosis following UUO in rats.