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Renal fibrosis is an outcome of chronic kidney disease, independent of the underlying etiology. Renal fibrosis is caused primarily by oxidative stress and inflammation. We identified the components of Plantaginis semen and elucidated their anti-fibrotic and anti-inflammatory mechanisms. The renoprotective components and underlying molecular mechanisms of P. semen were investigated in rats with adenine-induced chronic tubulointerstitial nephropathy (TIN) and in idole-3-acetic acid (IAA)-stimulated NRK-52E cells. Acetate and n-butanol extracts were found to be the bioactive fractions of P. semen. A total of 65 compounds including geniposidic acid (GPA), apigenin (APG), and acteoside (ATS) were isolated and identified. Among the seven main extract components, treatment with GPA, APG, and ATS reduced the serum levels of creatinine and urea in TIN rats. Mechanistically, GPA ameliorated renal fibrosis through repressing aryl hydrocarbon receptor (AHR) signaling and regulating redox signaling including inhibiting proinflammatory nuclear factor kappa B (NF-ƙB) and its target gene products as well as activated antioxidative nuclear factor-erythroid-2-related factor 2 (Nrf2) and its downstream target gene products in both TIN rats and IAA-stimulated NRK-52E cells. The inhibitory effect of GPA on AHR, NF-Ƙb, and Nrf2 signaling were partially abolished in IAA-stimulated NRK-52E cells treated with CH223191 compared with untreated IAA-stimulated NRK-52E cells. These data demonstrated that GPA alleviates oxidative stress and inflammation partly by suppressing AHR signaling.

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BACKGROUND: Lithium carbonate is commonly used in the treatment of bipolar disorder. A spectrum of side effects is associated with lithium, including nephrogenic diabetes insipidus, renal tubular acidosis, chronic tubulointerstitial nephropathy, and minimal change disease. Although the former three adverse effects are well-known, minimal change disease is relatively rare. CASE PRESENTATION: We herein report a case of lithium therapy-induced minimal change disease with concurrent chronic tubulointerstitial nephropathy. A 66-year old man with bipolar disorder treated by lithium for 20 years, presented to the hospital with anasarca and decreased urine output for 4 weeks. The medical history also included hyperlipidemia, hypertension, and benign prostatic hyperplasia. Further laboratory investigation revealed elevated serum lithium (2.17 mmol/L), potassium (6.0 mmol/L), and creatinine levels (2.92 mg/dL), nephrotic range proteinuria, and hypoalbuminemia. Lithium was discontinued and the patient was treated with intravenous fluids. He underwent a kidney biopsy, which showed findings consistent with minimal change disease with concurrent acute tubular injury and chronic tubulointerstitial nephropathy. The patient was subsequently treated with steroids in an outpatient setting. He did not respond to the treatment, and hemodialysis was started. CONCLUSION: Based on the previously reported cases and review of literature, occurrence of lithium-associated minimal change nephropathy is rare. Patients with lithium-associated minimal change disease and acute tubular injury usually respond to discontinuation of lithium therapy and/or steroid treatment. In this case, minimal change nephropathy was steroid-resistant and kidney function of the patient reported here did not recover after 6-month follow-up. We postulated the underlying cause to be minimal change disease with chronic tubulointerstitial nephropathy due to long-term lithium use. This case provides an example of a rare side effect of lithium-induced minimal change nephropathy with chronic tubulointerstitial nephropathy in addition to its well-known complication of interstitial nephritis or diabetes insipidus. In our opinion, these patients likely have much worse clinical outcome.

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Chronic tubulointerstitial nephropathy (CTIN) is one of the most common kidney diseases. However, treatment for CTIN has multiple limits. Adjuvant therapy through nutritional regulation has become a hot research topic at present. Icariin (ICA), an extraction of Chinese herbal medicine epimedium, has many pharmacological functions including anti-inflammation and tonifying kidney. Selenomethionine (SeMet) possesses the effects of antioxidant and lightening nephrotoxicity. However, little is known about the combined nephroprotection of them. This study was investigated to evaluate the joint effects of ICA and SeMet on CTIN and explore the mechanism. Based on a novel CTIN model developed in our previous study, mice were randomly divided into five groups (a: control; b: model; c: model + ICA; d: model + SeMet; e: model + ICA + SeMet). Renal tubule epithelial cells were treated with cyclosporine A and ochratoxin A without/with ICA or/and SeMet. The results showed that ICA or/and SeMet ameliorated CTIN by inhibiting the uptrends of blood urine nitrogen, serum creatinine, urine protein, urine gravity, histopathological damage degree and collagen I deposition. ICA or/and SeMet also increased cell proliferation and decreased apoptosis and the expression of transforming growth factor-beta 1 and α-smooth muscle actin. Emphatically, ICA and SeMet joint had better nephroprotection than alone in most indexes including fibrosis. Furthermore, ICA and SeMet joint decreased the activation of toll-like receptor 4 (TLR4)/NFκB pathway induced by CTIN. TLR4 overexpression counteracted the joint protection of ICA and SeMet. Therefore, ICA and SeMet in combination could protect against CTIN through blocking TLR4/NFκB pathway. The study will provide novel insights to explore an adjuvant therapeutic orientation.

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Besides its efficiency, lithium has a narrow therapeutic index and can result in considerable toxicity. Among the potential side effects, two types of renal toxicity are observed: a decreased renal concentrating ability and a chronic renal failure. Lithium-induced polyuria is frequent, estimated to affect up to 40% of patients, and develops usually early. It may be irreversible, especially if the treatment has been prescribed for more than 15 years. A chronic renal failure is observed in patients treated for more than 10 to 20 years. Its prevalence is estimated at 12% after 19 years of treatment. Some patients (0.5%) may reach end stage renal disease. The major risk factor is the duration of exposure to lithium. Discussion about stopping or not lithium in case of renal failure needs multidisciplinary expertise and depends on psychiatric status and renal function.

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Lithium is a psychotropic agent which is widely employed in the psychiatric practice throughout the world. The therapeutic index of lithium is low and an acute intoxication may appear, which may lead to death or a permanent disability. A frequent side effect of lithium is renal toxicity. The collecting tubules have been identified as the site of action of lithium, due to the down regulation of Acquaporin-2. The mast cells have been associated with a wide range of human renal diseases. They have been documented to be associated with interstitial fibrosis and an impaired renal function. We are reporting a case of a 42 year old male who was admitted with a history of an altered sensorium of short duration. He had bipolar disorder and was on lithium. Investigations revealed a severely compromised renal function. The patient's condition worsened and he expired. A necropsy was performed. The kidneys and the lungs were subjected to a histopathological examination. The kidneys showed a significant Chronic Tubulointerstitial Nephropathy [CTIN] and a considerable glomerular pathology. Toludine blue [1%] staining demonstrated mast cells in the interstitium and the connective tissue of the renal pelvis. This appears to be the first time that mast cells were demonstrated in a case of lithium induced nephropathy in humans. It may be hypothesized that mast cells may possibly play a role in lithium induced nephropathy as a concurrent mechanism.

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Objective:To analyze the morbid risk factors of chronic tubulointerstitial nephropathy(CTN)with an unknown origin in Wenzhhou City.Method:810 residents in several big districts were investigated.652 subjects,which had complete data and were coincided with the inclusion standard,were analyzed by an unmatched case-control study.The case group contained 19 cases coincided with the diagnostic criteria for CTN with unknown causes.The controlled group contained 633 cases.Thirteen probable risk factors were selected to be investigated:age,sex,body height,body weight, occupation,education,allergic history,addiction to smoking or wine,family history,the respective exposure to heavy met- als,radioactive ray and poisons.A history of medications,including caulis aristolochiae manshuriensis,antipyretic analge- sic,antibiotics,etc.was also investigated.The odds ratio(OR)of CTN with an unknown origin caused by risk factors were calculated with Logistic regression analysis.The obtained data were investigated,and the risk factors were screened out. All the data were analyzed with SPSS 12.0.Result:The homogeneity test showed there was no significant difference in age, sex,occupation and education between the case and controlled groups.The exposure to heavy metals or caulis aristolochiae manshuriensis was screened as the valid risk factor of CTN with OR 17.50 and 103.594 respoetively(P