Primary hyperoxaluria type II and organ transplantation / 器官移植

Primary hyperoxaluria type Ⅱ (PH2) is an inherited disorder of the glyoxylate metabolism caused by the gene mutation of glyoxylate reductase/hydroxypyruvate reductase (GRHPR). PH2 is characterized by recurrent nephrolithiasis and nephrocalcinosis, which may even progress into end-stage renal disease. Currently, organ transplantation is the only treatment option for PH2, which mainly includes two strategies: kidney transplantation and combined liver and kidney transplantation. Kidney transplantation yields a high risk of recurrence of oxalate nephropathy, which may cause early graft dysfunction. Combined liver and kidney transplantation could mitigate the deficiency of oxalate metabolism, whereas it yields a high risk of graft complications. PH2 is an extremely rare disorder. No consensus has been reached on the indications, surgical selection and perioperative management of organ transplantation for PH2 patients. In this article, the pathogenesis, diagnosis, monitoring and organ transplantation experience of PH2 were reviewed, aiming to divert clinicians' attention to PH2 and provide reference for determining diagnosis and treatment regimens, especially transplantation strategy for PH2 patients.

Summary of clinical characteristics, diagnosis and treatment of primary hyperoxaluria type 1 in mainland China / 器官移植

Objective To investigate the clinical manifestations, treatment and prognosis of primary hyperoxaluria type 1 (PH1). Methods Relevant literature review was conducted from Chongqing VIP, CNKI, Wanfang Data, PubMed, Web of Science, Embase and Cochrane databases. Clinical data of 57 patients with PH1 were collected, and the clinical manifestations, diagnosis and treatment and prognosis were analyzed. Results A total of 35 eligible studies were searched, including 57 patients with PH1, 39 male and 18 female, aged 0.2-57.0 years old, and the age of onset was from date of birth to 42 years old. The specificity of clinical symptoms of 57 patients with PH1 was relatively low, including 41 cases of renal stones, 21 cases of renal calcification and/or calcium deposition, 12 cases of oxalic acid deposition outside the urinary system, 12 cases of lumbago, backache and abdominal pain, and 8 cases of ureteral stones. Besides, alternative symptoms, such as decreased urine output, metabolic acidosis, disorder of water and electrolyte, anemia and gross hematuria were also reported. Thirty-three patients were diagnosed with end-stage renal disease (ESRD) upon admission. Twenty-six patients received transplantation. Among them, 17 cases underwent kidney transplantation (2 cases repeatedly received combined liver-kidney transplantation due to recurrence of stones and resumption of dialysis, and 1 case repeatedly received liver transplantation due to resumption of dialysis), 7 cases received combined liver-kidney transplantation, 2 cases underwent liver transplantation, and 3 cases received sequential liver-kidney transplantation, respectively. Thirty-one patients did not undergo transplantation. Significant differences were observed in the survival rate between patients treated with and without transplantation (85% vs. 58%, P < 0.05). Conclusions Clinical manifestations of PH1 are diverse and lack of specificity. A majority of PH1 patients are diagnosed with ESRD upon admission. Clinical prognosis of patients undergoing transplantation is better than that of those counterparts without transplantation. Prior liver transplantation or combined liver-kidney transplantation is recommended.

Simultaneous use of oxalate-degrading bacteria and herbal extract to reduce the urinary oxalate in a rat model: A new strategy

ABSTRACT Objective: Urinary stones with oxalate composition can cause kidney failure. Recent findings evidenced that probiotics are effective in reducing oxalate absorption in these subjects based on their high colonic absorption levels at baseline. The purpose of this study was to evaluate the effect of the simultaneous use of oxalate-degrading bacteria, Urtica dioica and T. terrestris extract in reducing urinary oxalate. Materials and Methods: Anti-urolithiatic activity of Urtica dioica and T. terrestris extract and probiotic by using ethylene glycol induced rat model. In this study, 4 strains of Lactobacillus and 2 strains of Bifidobacterium and also 2 strains of L. paracasei (that showed high power in oxalate degrading in culture media) were used. Male Wistar rats were divided into four groups (n=6). The rats of group-I received normal diet (positive control group) and groups-II (negative control group), III, IV rats received diet containing ethylene glycol (3%) for 30 days. Groups III rats received Urtica dioica and T. terrestris extract. Groups IV rats received extracts + probiotic for 30 days. Findings: The results show that the use of herbal extracts (Urtica dioica and T. terrestris) reduced the level of urinary oxalate and other parameters of urine and serum. Also, the accumulation of calcium oxalate crystals in the kidney tissue was significantly reduced. Conclusion: Considering that the formation of calcium oxalate crystals can cause inflammation and tissue damage in the kidney, the use of herbal extracts with oxalate degrading bacteria can be a new therapeutic approach to preventing the formation of kidney stones.

Anti-urolithiatic activity of sambong (Blumea balsamifera) extract in Ethylene Glycol-induced Urolithiatic Wistar Rats (Rattus norvegicus)

Objective@#The study aimed to determine if Blumea balsamifera inhibits calcium oxalate stone formation in the kidneys through determination of the number of calcium oxalate stones in the renal cortex and the percent mass of calcium oxalate.@*Methods@#Post-test only control group design was used using five treatment groups with placebo as the negative control, potassium citrate as the positive control, and 50%, 100%, and 200% sambong treatment. Urolithiasis was induced through ethylene glycol and ammonium chloride. Each treatment group was administered its corresponding treatment solution once daily for twenty-one days. Histopathologic examination and kidney homogenate analysis were done to determine the degree of deposition of calcium oxalate stones in renal tissues and the oxalate content, respectively. Statistical analyses were performed using one-way ANOVA and post hoc Gabriel's Pairwise Comparisons Test.@*Results@#The 100% sambong treatment group showed the least mean number of stones while the positive control and 50% sambong treatment group exhibited the highest anti-urolithiatic activity in terms of oxalate content of the kidney homogenate.@*Conclusion@#It can be concluded from the study that Blumea balsamifera inhibits calcium oxalate stone formation in the kidneys with the 100% and 50% sambong treatment most effective in decreasing number of stones and oxalate content of the kidney homogenate, respectively.

A study on biochemical composition in females with urolithiasis in southern part of Chennai

Background: Urinary stone constitutes one of the commonest diseases in our country. In India, approximately 5-7 million population suffer from stone disease and at least 7-10 per 1000 of Indian population needs hospitalization due to a kidney stone. It has been proposed that comorbidity with essential hypertension, overweight and Type 2 Diabetes Mellitus predispose to kidney stone disease. Few lithogenic risk factors like urinary calcium, oxalate and uric acid excretion, are known to be influenced by the rich animal protein diet, which in turn is frequently related to overweight. In a female patient with basal metabolic index (BMI), 40% higher than standard, there was an (89%) increase in the prevalence of kidney stone. The aim of the study: To diagnosis the different biochemical composition in women who were diagnosed with urolithiasis. Materials and methods: This observational study was done in 2018 at, Department of Urogynecology, Institute of Social Obstetrics, Government Kasturba Gandhi Hospital, Chennai. Chemical methods were used to perform stone analysis. Calculi were thoroughly washed with tap water to remove attached debris. Then they were rinsed with deionized water and air dried for two weeks in a plastic container. Once the calculi were dry, they were weighed and then grounded to a fine powder using mortar and pestle. These powdered calculi were used for qualitative and quantitative analysis. Results: According to the results, all calculi had oxalic acid and uric acid which were the commonest components in calculi. Calcium and phosphorous were the next common components followed by T. Srikala Prasad, A. Anandi. A study on biochemical composition in females with urolithiasis in southern part of Chennai. IAIM, 2019; 6(3): 243-247. Page 244 magnesium. Ammonium ion was detected in 59.5% renal calculi. None of the calculi contained carbonate or cysteine. Conclusion: Factors like diet and lifestyle plays an important role in the changing epidemiology of kidney stone. Changes in two of the most important environmental factors, diet, and climate, are the significant impact on these trends. Patients who had raised serum calcium and serum uric acid level had larger and multiple calculi bilaterally. There is strong evidence that diminished fluid and dietary calcium consumption is a risk factor and an increase in animal protein intake has an equal impact on kidney stone risk.

Correlation between clusterin expression and recurrence of calcium oxalate kidney stone / 第二军医大学学报

Objective To investigate the risk factors influencing the recurrence of calcium oxalate kidney stone. Methods The clinical data of patients with calcium oxalate kidney stone were collected; they were hospitalized in Changhai Hospital, Navy Medical University (Second Military Medical University) from Sep. 2015 to Dec. 2015. The patients were divided into the first-time calcium oxalate stone group (first-time group) and the recurrent of calcium oxalate stone group (recurrent group) according to the stone histories. The concentrations of clusterin in serum and urine, and the concentrations of serum interleukin (IL)-1β, IL-2 and IL-6 in the two groups were detected by ELISA. The independent risk factors influencing the recurrence of calcium oxalate kidney stones were analyzed by univariate and multivariate logistic regression analysis. Results Thirty-six patients were included in each group. Univariate analysis showed that there were no significant differences in age, gender, body mass index (BMI), estimated glomerular filtration rate (eGFR), maximum stone diameter or the concentrations of serum clusterin, IL-1β, IL-2 and IL-6 between the two groups (all P0.05). The concentration of urinary clusterin in the recurrent group was significantly lower than that in the first-time group ([44.35±15.44] ng/mL vs [56.76±16.80] ng/mL, t=–3.262, P0.05). Multivariate logistic regression analysis showed that urinary clusterin concentration (OR=0.939, 95% CI 0.900-0.979, P0.05) was an independent risk factor influencing the recurrent of calcium oxalate kidney stone. Conclusion The concentration of urinary clusterin is decreased in patients with recurrence of calcium oxalate stone compared the first-time stone patients, suggesting that the clusterin in urine may be closely related to the recurrence of stones.

Effect of autophagy inhibitor chloroquine on the renal calcium oxalate crystals formation in rats / 中华泌尿外科杂志

Objective To investigate the effect and potential mechanism of autophagy inhibitor chloroquine on the calcium oxalate crystals formation in rats.Methods From September 2016 to October 2016,Thirty healthy male SD rats were randomly divided into 3 groups:control group,model group and chloroquine intervention group.The method to establish calcium oxalate stone model was drinking water with 1％ ethylene and 1％ ammonium chloride freely.The rats of chloroquine intervention group were treat with chloroquine (40mg/kg · d) by intraperitoneal injection.Modeling was finished after 28 days.The amounts of renalcalcium oxalate crystals were detected by polarizing microscope.For all groups,the amounts of autophagosome were detected by transmission electron microscope.Twenty four hour urine compositions for stone risk factors were detected.The expressions of oxidative stress injury related molecular markers (SOD,MCP-1 and 8-OHdG) and the expressions of autophagy markers (LC3 and P62) were detected by immunohistochemistry.The RNA expressions of SLC26A6 in kidney were detected by Real-time PCR.Results Compared to the model group,the amounts of renal calcium oxalate crystals were significantly reduced in chloroquine intervention group (32.37 ± 5.14 vs.4.18 ± 0.25,P ＜ 0.05).Compared to the control group,the level of autophagy was increased in the model group.Compared to the model group,the level of autophagy was inhibited in the chloroquine intervention group.For control group,model group and chloroquine intervention group,the excretion of urinary oxalate were (3.1 ± 1.5) mmol,(22.5 ± 8.1) mmol,(2.8 ± 1.2) mmol,respectively;the excretion of urinary citrate were (63.4 ± 7.4) mmol,(45.9 ± 9.5)mmol,(15.6 ± 8.2) mmol,respectively.Compared to the control group,the amounts of urinary oxalate weresignificantly elevated in model group (P ＜ 0.05),but citrate were significantly reduced in the chloroquineintervention group(P ＜ 0.05).For control group,model group and chloroquine intervention group,theexpressions of SOD were 42.24 ±4.16,19.21 ± 2.25,39.08 3.53,respectively;the expressions of MCP-1 were 4.02 0.51,8.45 ± 0.55,5.52 ± 0.34,respectively;the expressions of 8-OHdG were 7.16 ± 0.54,11.21 ± 1.12,8.67 ±0.34,respectively;the RNA expressions of SLC26A6 were 0.35 ±0.07,1.02 ±0.17,0.70 ± 0.06,respectively.Compared to the control group,the expressions of SOD were significantly reduced in the model group,but the expressions of MCP-1,8-OHdG and SLC26A6 were significantly elevated(P ＜0.05).Compared to the model group,the expressions of SOD were significantly elevated chloroquine intervention group (P ＜ 0.05),but the expressions of MCP-1,8-OHdG and SLC26A6 were significantly elevated(P ＜ 0.05).Conclusions The autophagy inhibitor chloroquine could inhibit the formation of calcium oxalate crystals induced by ethylene in rat kidney via inhibit the renal autophagy level and expressions of the SLC26A6,reducing the renal oxidative stress injury and urinary oxalate excretion.

Effect of Klotho protein on renal oxidative stress in rat with calcium oxalate nephrolithiasis / 中华泌尿外科杂志

Objective To investigate the protective effect and mechanism of Klotho protein on oxidative stress in renal tubular epithelial cells of experimental rat nodels of renal calcium oxalate stone.Methods The 30 SD rats,6-8 weeks old,were randomly divided into 3 groups (10 of each),normal control group(group A),calcium oxalate model group(group B),drug plus calcium oxalate model group (group C).Group A was established with physiological saline by garage each day,group B was established with 1％ ethylene glycol in drinking water + 2％ ammonium chloride by garage (2 ml/d),group C was established with Fosinopril 2.5mg + Valsartan 15mg aqueous solution 2 ml by gavage on the basis of group B (2 ml/d).4 weeks later,the level of malondialdehyde (MDA),superoxide dismutase (SOD),catalase (CAT) and glutathione peroxidase (GSH) in the kidney homogenate were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA),Polymerase chain reaction (RT-PCR) was used to measure expression of Klotho and Nrf2 mRNA,and Western Blot was used to measure the expression of Klotho and Nrf2 protein.Results The level of MDA in group B [(12.43 ± 0.43) μmol/mg] was significantly increased compared to group A[(8.67 ±0.84) μmol/mg,P ＜0.05] and group C [(7.97 ±0.81) μmol/mg,P＜0.05],while group A was close to group C (P ＞0.05).In group A,B,and C,the levels of SOD were (247.89 ± 2.45),(109.54 ± 4.21),and (189.74 ± 10.47) U/mg,respectively;the levels of GSH were (38.98 ± 4.55),(26.87 ± 3.92),and (31.29± 2.54) μmol/mg,respectively;CAT were (138.47 ± 8.74),(119.87 ± 8.45),and (127.46 ± 7.45) U/mg,respectively.The levels of SOD,GSH,CAT in group B were significantly lower than that in group A and C,while those in group B were close to group A (P ＞ 0.05).The expression of Klotho and Nrf2 mRNA in group B [(0.208 ± 0.036) and (0.499 ± 0.086)] were significantly lower than group A (1.011 ± 0.174 and 1.023 ± 0.139,P ＜ 0.05)and group C(1.123 ±0.248 and 1.023 ±0.139,P ＜0.05).The expression of Klotho and Nrf2 protien were also significantly lower than that in group A and C (P ＜0.05).Conclusions Valsartan and Fosinopril could prevent the formation of renal CaOx stones by upregulating expression of low level Klotho gene induced by ethylene glycol.This effect may be involved with activation of Keapl-Nrf2-ARE signaling pathway.

Study on the effect and mechanism of total flavones of plantago asiatica for rats with calcium oxalate stone in kidney / 中国生化药物杂志

Objective To explore the effect and mechanism of total flavones of plantago asiatica for rats with calcium oxalate stone in kidney. Methods 50 rats were divided into control group, model group, total flavones of Plantago asiatica high dose group, total flavones of Plantago asiatica low dose group and positive drug group. Made the model rats with calcium oxalate stone in kidney. Rats in total flavones of plantago asiatica group were intervened by total flavonoids of plantago asiatica, the positive drug group was given puerarin intervention and continuous intervention for 28 days. The pathology of the kidneys, the levels of oxalate and Ca2 in urine, the superoxide dismutase (SOD) and malondialdehyde (MDA) in serum, and osteopontin in the kidneys were examined. Results There were dilated renal tubules and necrosis of renal tubular epithelial cells in total flavones of plantago asiatica group, but the extent of renal tubular cells was significantly improved. The urine oxalate and Ca2 levels, serum MDA levels, and osteopontin levels in the kidney in the total flavonoids of Plantago high dose group, the total flavonoids of Plantago low dose group, positive drug group were significantly lower than that in model group (P<0.05), and serum SOD level was significantly higher than that in model group (P<0.05) . The urine oxalate and Ca2 levels, serum MDA levels, and osteopontin levels in the kidney in the total flavonoids of Plantago high dose group were significantly lower than that in the total flavonoids of Plantago low dose group (P<0.05), and serum SOD level was significantly higher than that in the total flavonoids of Plantago low dose group (P<0.05) . There was no significant difference between the total flavonoids of Plantago high dose group and the positive drug group for above indexes. Conclusions The total flavonoids of pantago asiatica can inhibit the formation of renal calcium oxalate stone, and its mechanism may be the antioxidant stress and the inhibition of osteopontin expression.

Study on the effect and mechanism of total flavones of plantago asiatica for rats with calcium oxalate stone in kidney / 中国生化药物杂志

Objective To explore the effect and mechanism of total flavones of plantago asiatica for rats with calcium oxalate stone in kidney. Methods 50 rats were divided into control group, model group, total flavones of Plantago asiatica high dose group, total flavones of Plantago asiatica low dose group and positive drug group. Made the model rats with calcium oxalate stone in kidney. Rats in total flavones of plantago asiatica group were intervened by total flavonoids of plantago asiatica, the positive drug group was given puerarin intervention and continuous intervention for 28 days. The pathology of the kidneys, the levels of oxalate and Ca2 in urine, the superoxide dismutase (SOD) and malondialdehyde (MDA) in serum, and osteopontin in the kidneys were examined. Results There were dilated renal tubules and necrosis of renal tubular epithelial cells in total flavones of plantago asiatica group, but the extent of renal tubular cells was significantly improved. The urine oxalate and Ca2 levels, serum MDA levels, and osteopontin levels in the kidney in the total flavonoids of Plantago high dose group, the total flavonoids of Plantago low dose group, positive drug group were significantly lower than that in model group (P<0.05), and serum SOD level was significantly higher than that in model group (P<0.05) . The urine oxalate and Ca2 levels, serum MDA levels, and osteopontin levels in the kidney in the total flavonoids of Plantago high dose group were significantly lower than that in the total flavonoids of Plantago low dose group (P<0.05), and serum SOD level was significantly higher than that in the total flavonoids of Plantago low dose group (P<0.05) . There was no significant difference between the total flavonoids of Plantago high dose group and the positive drug group for above indexes. Conclusions The total flavonoids of pantago asiatica can inhibit the formation of renal calcium oxalate stone, and its mechanism may be the antioxidant stress and the inhibition of osteopontin expression.

Expression of the nod-like receptor protein 3 inflammasome in calcium oxalate stone kidney / 中华泌尿外科杂志

Objective To explore the expression level and significance of the nod-like receptor protein 3 (NLRP3) inflammasome in renal tissue with calcium oxalate stone.Methods 20 kidney specimens were collected as the experimental group from patients with calcium oxalate stone who underwent nephrectomy because of stones in our hospital between January 2008 and December 2014;another 20 renal specimens were get as the control group from patients with renal carcinoma,the renal tissues were obtained 2cm far from the tumor and proved as normal tissue.Immunohistochemical detection was carried out to analyze the expression level of NLRP3,Caspase-1,and IL-1β in the 40 renal samples.Animal experiment:fourteen male SD rats were randomly divided into calcium oxalate stone group and control group.For calcium oxalate stone group we established an ethylene glycol method induced hyperoxaluric rat model featured by crystalline material within tubule lumens;for control group normal feeding was performed.After 6 weeks,all rats were sacrificed,and the kidneys were harvested for further experiments.HE staining and Pizzolato staining were used to detect calcium oxalate crystals within tubule lumens.Western boltting and RT-PCR was applied to detect protein level and mRNA quantity of NLRP3,Caspase-1,and IL-1β from tissue lysates in rat model.Results In renal tissue samples obtained from patients with calcium oxalate stone disease,we demonstrated that the expression level of NLRP3,Caspase-1,and IL-1β were above to the normal renal tissue samples.We established a hyperoxaluric rat model character with crystalline material within tubule lumens examined by renal histology with HE staining and Pizzolato staining.And we detected that the protein and mRNA levels of NLRP3,Caspase-1 and IL-1β were remarkably increased in the lysates from the hyperoxaluric rat model (P ＜ 0.05).Conclusions The NLRP3 inflammasome has overexpression in the renal tissue of patients with calcium oxalate stone as well as in the renal tissue of hyperoxaluric rat,and it provides a new thought to reveal the formation of calcium oxalate stone.

Effect of Male Sex Hormones on Calcium Oxalate Nephrolithiasis in Ethylene Glycol-Treated Rats / 대한비뇨기과학회지

PURPOSE: Sexual differences in the incidence and crystalline composition of urinary stones in humans are well-known, but it is unclear why men have a higher incidence of calcium oxalate stones than women. We investigated the effects of male sex hormones on stone formation using an ethylene glycol (EG) - induced urolithiasis model in rats. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were divided into 4 groups, each containing 10 rats. One group of rats was left untreated and served as control. The other 3 groups were fed a 1% ethylene glycol (EG) lithogenic diet for 4 weeks. Among these, one group was non-castrated, one group was castrated and one group was non-castrated and given finasteride orally. Serum testosterone, creatinine, electrolytes, 24-hour urine levels of oxalate and citrate, and creatinine clearance were measured. The crystal deposits were examined by light and polarizing microscopes. RESULTS: Testosterone promoted calcium oxalate stone formation in EG - treated rats. Finasteride administration significantly decreased urinary oxalate excretion and calcium oxalate deposition, compared with controls. Urinary citrate was significantly decreased in EG-treated rats, but was not influenced by castration or administration of finasteride. There were no significant differences in serum concentrations of creatinine, sodium, or potassium among the control and experimental groups. CONCLUSIONS: Our data suggest that testosterone promotes calcium oxalate stone formation, and that dihydrotestosterone may be partially responsible for the exaggerated hyperoxaluria in EG-treated rats. Additionally, male sex hormones have a lesser influence on urinary citrate than oxalate.

Effects of Sex Hormones on Calcium Oxalate Nephrolithiasis in Ethylene Glycol-Treated Rats / 대한비뇨기과학회지

PURPOSE: Sexual differences in the incidence and crystalline composition of urinary stones in humans are well-known, but it is unclear why men have a higher incidence of calcium oxalate stones than women. We investigated the effects of sex hormones on stone formation using an ethylene glycol (EG)-induced urolithiasis model in rats. MATERIALS AND METHODS: Adult Sprague-Dawley rats were divided into 13 groups of 10 each, segregated by sex. Two groups of rats were untreated to serve as male and female controls. The other 11 groups were fed a 1% EG lithogenic diet for 4 weeks. Among these, 2 groups were males and females otherwise not treated; two groups were neutered with bilateral orchiectomies or oophorectomies as appropriate; two groups were neutered and received subcutaneous testosterone; 2 groups were neutered and received subcutaneous estradiol; 2 groups were intact males and females administered the opposite sex hormone; and 1 group was intact males given finasteride orally. Serum testosterone, estrogen, creatinine, electrolytes, 24-hour urine levels of oxalate and citrate, and creatinine clearance were measured. The crystal deposits were examined by light and polarizing microscopes. RESULTS: Exogenous testosterone promoted, whereas estrogen inhibited, calcium oxalate stone formation in EG-treated rats. Finasteride administration significantly decreased urinary oxalate excretion and calcium oxalate deposition, compared with controls. Urinary citrate was significantly decreased in EG-treated female rats, but was not influenced by neutering and/or exogenous sex hormones in either sex. There were no significant differences in serum concentrations of creatinine, sodium, or potassium among the control and experimental groups. CONCLUSIONS: Our data suggest that testosterone promotes and estrogen inhibits calcium oxalate stone formation, and that dihydrotestosterone may be partially responsible for the exaggerated hyperoxaluria in EG-treated rats. Additionally, sex hormones have a lesser influence on urinary citrate than oxalate.