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2.
Am J Dermatopathol ; 44(12): 981-983, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36395453

RESUMO

ABSTRACT: A 19-year-old girl presented to the emergency department with a progressively painful purpuric lesion on the left dorsal foot, which had initially appeared 2 days prior. Three months earlier, she had been diagnosed with end-stage renal disease. Her medical history also included recurrent urolithiasis for the past 5 years and liver failure. Biopsy revealed oxalate crystals occluding vessels with secondary epidermal and dermal ischemia. Oxalate crystals were also visualized in the vessel walls and free in the subcutis. Genetic testing confirmed the diagnosis of primary hyperoxaluria type 1. She was treated with sodium thiosulfate, apixaban, pentoxifylline, wound care, and palliative care. At 4-month follow-up, the cutaneous manifestations of oxalosis were confined to only her feet, and she was undergoing evaluation for combined liver and kidney transplant. Cutaneous oxalosis because of primary hyperoxaluria should be considered in young patients presenting with purpuric lesions, recurrent urolithiasis, and early-onset renal failure.


Assuntos
Hiperoxalúria Primária , Hiperoxalúria , Falência Renal Crônica , Urolitíase , Humanos , Feminino , Adulto Jovem , Adulto , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/terapia , Falência Renal Crônica/complicações , Urolitíase/complicações , Oxalatos
3.
Int Urol Nephrol ; 54(11): 2819-2825, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35917078

RESUMO

PURPOSE: American Urology Association guidelines recommend genetic testing for patients with recurrent stones and urine oxalate > 75 mg/day. The goal of this study was to examine the treatment of patients in this category in a large multidisciplinary adult stone clinic. METHODS: Patients were evaluated from a single institution between 2006 and 2019. Those with at least one level of urinary oxalate excretion (uOx) above 75 mg/day were identified. A chart review identified enteric risk factors and genetic testing results. Patients without an identifiable enteric cause were considered idiopathic. RESULTS: A total of 4229 separate 24-h urine collections in 1302 patients were reviewed. At least one measurement of uOx above 75 mg/day was found in 103 (7.9%) patients. Enteric hyperoxaluria (EH) was seen in 28 (27%) and idiopathic hyperoxaluria (IH) in 76 (74%). 20 (71%) patients in the EH group had undergone gastric bypass. The median uOx was significantly higher level in the EH group (121.0 vs. 93.0 mg/day). For the entire cohort, there was a drop in uOx (- 33.8 mg/day) with medical and dietary therapy after a follow-up of 46.6 months. The final oxalate was higher in EH (88.9 vs. 60.1 mg/day). Only one patient had referral for genetic testing and was found to have primary hyperoxaluria type 2. CONCLUSIONS: The most common cause of significant hyperoxaluria in patients with recurrent nephrolithiasis remains idiopathic. Patients with IH have more significant improvement in uOx compared to EH; however, both groups had hyperoxaluria at last follow-up. Rate of genetic testing is low despite guideline recommendations.


Assuntos
Hiperoxalúria , Cálculos Renais , Nefrolitíase , Adulto , Estudos de Coortes , Humanos , Hiperoxalúria/complicações , Hiperoxalúria/urina , Cálculos Renais/urina , Nefrolitíase/genética , Oxalatos/urina , Fatores de Risco
4.
Pediatr Transplant ; 26(8): e14380, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35979862

RESUMO

BACKGROUND: Although nephrolithiasis (NL) and nephrocalcinosis (NC) are very common features of primary hyperoxaluria type 1 (PH1), the long-term prognosis of NL and NC after preemptive liver transplantation (PLT) has not been elucidated. MATERIAL AND METHODS: We describe the cases of two chronic kidney disease (CKD) stage three patients with different clinical courses after PLT for PH1. RESULTS: The first patient underwent PLT at 7 years of age with an estimated glomerular filtration rate (eGFR) of 47.8 ml/min/1.73 m2 . Two years later, she experienced several episodes of obstructive pyelonephritis due to urolithiasis, and developed septic shock in one of these episodes. At the same time as these episodes, preexisting NL and NC progressively improved, with disappearance on X-ray disappeared at 8 years after transplantation. Her renal function has been maintained with an eGFR of 58.7 ml/min/1.73 m2 . The second patient received PLT at 10 years of age with an eGFR of 58.9 ml/min/1.73 m2 . Her renal function has been maintained with an eGFR of 65.9 ml/min/1.73 m2 . She had repeated urolithiasis which started to appear at 3 years after LT. The radiological findings still show bilateral NL and NC, but the stones in the renal pelvis have shown mild improvement. CONCLUSIONS: Regardless of the regression in NC seen on X-ray, long-term maintenance of the renal function in patients with PH1 with CKD stage 3 can be achieved with PLT. In patients with NL, there is a risk of serious complications due to posttransplant immunosuppressive therapy when obstructive pyelonephritis occurs after LT.


Assuntos
Hiperoxalúria Primária , Hiperoxalúria , Falência Renal Crônica , Transplante de Fígado , Nefrocalcinose , Nefrolitíase , Pielonefrite , Urolitíase , Humanos , Feminino , Nefrocalcinose/etiologia , Nefrocalcinose/complicações , Transplante de Fígado/efeitos adversos , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/cirurgia , Nefrolitíase/complicações , Nefrolitíase/diagnóstico , Urolitíase/complicações , Pielonefrite/complicações
5.
Urolithiasis ; 50(5): 557-565, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35976425

RESUMO

We examined how physicians made therapeutic choices to decrease stone risk in patients with bowel disease without colon resection, many of whom have enteric hyperoxaluria (EH), at a single clinic. We analyzed clinic records and 24-h urine collections before and after the first clinic visit, among 100 stone formers with bowel disease. We used multivariate linear regression and t tests to compare effects of fluid intake, alkali supplementation, and oxalate-focused interventions on urine characteristics. Patients advised to increase fluid intake had lower initial urine volumes (L/day; 1.3 ± 0.5 vs. 1.7 ± 0.7) and increased volume more than those not so advised (0.7 ± 0.6 vs. 0.3 ± 0.6 p = 0.03; intervention vs. non-intervention). Calcium oxalate supersaturation (CaOx SS) fell (95% CI -4.3 to -0.8). Alkali supplementation increased urine pH (0.34 ± 0.53 vs. 0.22 ± 0.55, p = 0.26) and urine citrate (mg/d; 83 ± 256 vs. 98 ± 166, p = 0.74). Patients advised to reduce oxalate (mg/day) absorption had higher urine oxalate at baseline (88 ± 44 vs. 50 ± 26) which was unchanged on follow-up (88 (baseline) vs. 91 (follow-up), p = 0.90). Neither alkali (95% CI -1.4 to 2.1) nor oxalate-focused advice (95% CI -1.2 to 2.3) lowered CaOx SS. Physicians chose treatments based on baseline urine characteristics. Advice to increase fluid intake increased urine volume and decreased CaOx SS. Alkali and oxalate interventions were ineffective.


Assuntos
Hiperoxalúria , Cálculos Renais , Álcalis , Oxalato de Cálcio/urina , Humanos , Hiperoxalúria/complicações , Hiperoxalúria/terapia , Hiperoxalúria/urina , Cálculos Renais/etiologia , Cálculos Renais/prevenção & controle , Cálculos Renais/urina , Oxalatos
6.
Cells ; 11(15)2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35954150

RESUMO

Urolithiasis is a worldwide problem and a risk factor for kidney injury. Oxidative stress-associated renal endothelial dysfunction secondary to urolithiasis could be a key pathogenic factor, similar to obesity and diabetes-related nephropathy. The aim of the present study was to characterize urolithiasis-related endothelial dysfunction in a hyperoxaluria rat model of renal lithiasis. EXPERIMENTAL APPROACH: Endothelial dysfunction was assessed in preglomerular arteries isolated from control rats and in which 0.75% ethylene glycol was administered in drinking water. Renal interlobar arteries were mounted in microvascular myographs for functional studies; superoxide generation was measured by chemiluminescence and mRNA and protein expression by RT-PCR and immunofluorescence, respectively. Selective inhibitors were used to study the influence of the different ROS sources, xanthine oxidase, COX-2, Nox1, Nox2 and Nox4. Inflammatory vascular response was also studied by measuring the RNAm expression of NF-κB, MCP-1 and TNFα by RT-PCR. RESULTS: Endothelium-dependent vasodilator responses were impaired in the preglomerular arteries of the hyperoxaluric group along with higher superoxide generation in the renal cortex and vascular inflammation developed by MCP-1 and promoted by NF-κB. The xanthine oxidase inhibitor allopurinol restored the endothelial relaxations and returned superoxide generation to basal values. Nox1 and Nox2 mRNA were up-regulated in arteries from the hyperoxaluric group, and Nox1 and Nox2 selective inhibitors also restored the impaired vasodilator responses and normalized NADPH oxidase-dependent higher superoxide values of renal cortex from the hyperoxaluric group. CONCLUSIONS: The current data support that hyperoxaluria induces oxidative stress-mediated endothelial dysfunction and inflammatory response in renal preglomerular arteries which is promoted by the xanthine oxidase, Nox1 and Nox2 pathways.


Assuntos
Hiperoxalúria , Urolitíase , Animais , Artérias/metabolismo , Hiperoxalúria/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , RNA Mensageiro/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo , Xantina Oxidase/metabolismo
7.
Physiol Rep ; 10(14): e15357, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35851836

RESUMO

Ob/ob mice have recently emerged as a model for obesity-related hyperoxaluria as they are obese and excrete more urine oxalate compared to wild type mice. Ob/ob mice are deficient of leptin and develop obesity with hyperphagia and hyperinsulinemia. We hypothesized that insulin resistance and the gut microbiome contribute to hyperoxaluria in ob/ob mice. We developed a new liquid chromatography-mass spectrometry assay for urine oxalate and first compared urine oxalate excretion in ob/ob mice before and after ablation of intestinal bacteria with a standard antibiotic cocktail. We then compared urine oxalate excretion in ob/ob mice before and after leptin replacement or pioglitazone treatment, two maneuvers that reduce insulin resistance in ob/ob mice. Ob/ob mice excreted more oxalate into the urine in a 24-h period compared to wild type mice, but antibiotic, leptin, or pioglitazone treatment did not change urine oxalate excretion in ob/ob mice. Unexpectedly, we found that when food intake was carefully matched between ob/ob and wild type mice, the amount of 24-h urine oxalate excretion did not differ between the two mouse strains, suggesting that ob/ob mice excrete more urine oxalate because of hyperphagia. Since the level of urine oxalate excretion in wild type mice in our study was higher than those reported in prior studies, future work will be needed to standardize the measurement of urine oxalate and to define the range of urine oxalate excretion in wild type mice so that accurate and valid comparisons can be made between wild type mice and ob/ob mice or other mouse models.


Assuntos
Microbioma Gastrointestinal , Hiperoxalúria , Resistência à Insulina , Oxalatos , Animais , Antibacterianos/farmacologia , Hiperoxalúria/etiologia , Hiperoxalúria/urina , Hiperfagia/urina , Leptina , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Obesos , Obesidade/microbiologia , Obesidade/urina , Oxalatos/urina , Pioglitazona/farmacologia
9.
BMJ Case Rep ; 15(7)2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35787489

RESUMO

A kidney transplant recipient with a medical history of type 1 diabetes mellitus (T1DM) presents to the clinic with an acute kidney injury (AKI) and diarrhoea. Kidney biopsy found deposition of focal oxalate crystals, and further investigation revealed a raised 24-hour urinary oxalate and reduced faecal elastase. Therefore, we present a case of acute oxalate nephropathy (AON) secondary to enteric hyperoxaluria as a result of pancreatic insufficiency caused by T1DM. T1DM is a common cause of end-stage renal failure and exocrine pancreatic insufficiency. Therefore, AON secondary to enteric hyperoxaluria should be considered in patients with a transplant AKI. Earlier testing of 24-hour urinary oxalate and faecal elastase could generate diagnosis before biopsy results and allow commencement of pancreatic replacement therapy earlier to avoid permanent loss of kidney function.


Assuntos
Injúria Renal Aguda , Diabetes Mellitus Tipo 1 , Insuficiência Pancreática Exócrina , Hiperoxalúria , Injúria Renal Aguda/complicações , Diabetes Mellitus Tipo 1/complicações , Insuficiência Pancreática Exócrina/complicações , Humanos , Hiperoxalúria/complicações , Hiperoxalúria/diagnóstico , Rim , Oxalatos/urina , Elastase Pancreática
10.
Ren Fail ; 44(1): 1134-1143, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35837686

RESUMO

INTRODUCTION AND OBJECTIVE: To examine the dynamic changes in the formative factors of nephrolithiasis and the final micromorphological changes in an obesity-initiated metabolic syndrome (MS) rat model. METHODS: Forty five-week-old male Sprague-Dawley (SD) rats were randomly divided into four groups: the regular diet group (RD), high-fat diet group (HFD), regular diet with drug (ethylene glycol and ammonium chloride) group (RDD), and high-fat diet with drug group (HFDD). A dynamic assessment of MS components (body weight (BW), body length (BL), Lee's index (LI), blood glucose (BG), total cholesterol (TC), and triglycerides (TGs)) and stone-forming factors (urinary pH, urinary calcium, and urinary oxalate acid) was carried out. In addition, the levels of oxidative stress (OS) markers (CAT, SOD, TAC, GSH-PX, and MDA) were measured, and histological analysis was carried out at the end of 16 weeks. RESULTS: MS-related parameters, such as BW, LI, BG, TC, and TG, were significantly higher in HFD-fed rats than in RD-fed rats (p < 0.001). In the HFDD group, significantly lower urinary pH, hyperoxaluria, and hypocalciuria were noted in the dynamic assessment of stone-forming factors (p < 0.001). CAT, TAC, and MDA were notably changed in the HFD-fed groups, particularly the HFDD rats. Histological analysis showed that the renal tubules of HFDD rats had the highest scores for both inflammation and renal crystallization deposition (p < 0.05). CONCLUSIONS: Our results suggest that male SD rats with MS are prone to developing nephrolithiasis. Validation in an in vivo model may lead to an understanding of the underlying pathophysiological mechanisms of action of MS-related nephrolithiasis in humans.Key messagesMale SD rats with metabolic syndrome are more prone to developing calcium oxalate nephrolithiasis after treatment with ethylene glycol and ammonium chloride compared to control lean rats.MS-related nephrolithiasis in rats induced by ethylene glycol and ammonium chloride is mainly related to increased hyperoxaluria and inflammation and decreased antioxidant levels.High-fat diet-fed SD rats treated with ethylene glycol and ammonium chloride are a stable and valid in vivo model for understanding the potential mechanism of action of MS-related nephrolithiasis.


Assuntos
Hiperoxalúria , Cálculos Renais , Síndrome Metabólica , Nefrolitíase , Cloreto de Amônio/efeitos adversos , Animais , Etilenoglicol/efeitos adversos , Humanos , Hiperoxalúria/complicações , Inflamação , Cálculos Renais/etiologia , Masculino , Síndrome Metabólica/complicações , Nefrolitíase/induzido quimicamente , Ratos , Ratos Sprague-Dawley
11.
Indian J Pediatr ; 89(12): 1243-1250, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35819704

RESUMO

OBJECTIVE: To evaluate metabolic and genetic abnormalities in children with nephrolithiasis attending a referral center in North India. METHODS: The patients aged 1-18 y old with nephrolithiasis underwent biochemical evaluation and whole-exome sequencing. The authors evaluated for monogenic variants in 56 genes and compared allele frequency of 39 reported polymorphisms between patients and 1739 controls from the GenomeAsia 100 K database. RESULTS: Fifty-four patients, aged 9.1 ± 3.7 y were included. Stones were bilateral in 42.6%, familial in 33.3%, and recurrent in 25.9%. The most common metabolic abnormalities were hypercalciuria (35.2%), hyperoxaluria (24.1%), or both (11.1%), while xanthinuria (n = 3), cystinuria (n = 1), and hyperuricosuria (n = 1) were rare. Exome sequencing identified an etiology in 6 (11.1%) patients with pathogenic/likely pathogenic causative variants. Three variants in MOCOS and one in ATP7B were pathogenic; likely pathogenic variants included MOCOS (n = 2), AGXT, and SLC7A9 (n = 1, each). Causality was not attributed to two SLC34A1 likely pathogenic variants, due to lack of matching phenotype and dominant family history. Compared to controls, allele frequency of the polymorphism TRPV5 rs4252402 was significantly higher in familial stone disease (allele frequency 0.47 versus 0.53; OR 3.2, p = 0.0001). CONCLUSION: The chief metabolic abnormalities were hypercalciuria and hyperoxaluria. A monogenic etiology was identified in 11% with pathogenic or likely pathogenic variants using a gene panel for nephrolithiasis. Heterozygous missense variants in the sodium-phosphate cotransporter SLC34A1 were common and required evaluation for attributing pathogenicity. Rare polymorphisms in TRPV5 might increase the risk of familial stones. These findings suggest that a combination of metabolic and genetic evaluation is useful for determining the etiology of nephrolithiasis.


Assuntos
Hipercalciúria , Hiperoxalúria , Nefrolitíase , Humanos , Hipercalciúria/complicações , Hiperoxalúria/complicações , Índia , Nefrolitíase/genética , Fenótipo , Sulfurtransferases/genética , Criança
12.
Life Sci ; 305: 120786, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35809664

RESUMO

AIM: Urinary glycoproteins such as Tamm Horsfall Protein (THP) and Osteopontin (OPN) are well established key regulators of renal stone formation. Additionally, recent revelations have highlighted the influence of Endoplasmic Reticulum (ER) and mitochondria of crucial importance in nephrolithiasis. However, till date conclusive approach highlighting the influence of ER stress on urinary glycoproteins and chaperone in nephrolithiasis remains elusive. Therefore, the present study was focussed on deciphering the possible effect of 4-PBA mitigating ER stress on urinary glycoproteins and calnexin (chaperone) with emphasis on interlinking calcium homeostasis in hyperoxaluric rats. MATERIAL AND METHODS: Post 9 days of treatment, animals were sacrificed, and renal tissues were investigated for urinary glycoproteins, calnexin, calcium homeostasis, ER environment, redox status, and mitochondrial linkage. KEY FINDINGS: 4-PBA appreciably reversed the altered levels of THP, OPN, and calnexin observed along with curtailing the disrupted calcium homeostasis when assessed for SERCA activity and intra-cellular calcium levels. Additionally, significant improvement in the perturbed ER environment as verified by escalated ER stress markers, disturbed protein folding-aggregation-degradation (congo red assay) pathway, and redox status was found post 4-PBA intervention. Interestingly, linkage of ER stress and mitochondria was established under hyperoxaluric conditions when assessed for protein levels of VDAC1 and GRP75. SIGNIFICANCE: 4-PBA treatment resulted in rectifying the repercussions of ER-mitochondrial caused distress when assessed for protein folding/aggregation/degradation events along with disturbed calcium homeostasis. The present study advocates the necessity to adopt a holistic vision towards hyperoxaluria with emphasis on glycoproteins and ER environment.


Assuntos
Hiperoxalúria , Cálculos Renais , Animais , Butilaminas , Cálcio/metabolismo , Calnexina/metabolismo , Calnexina/farmacologia , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Glicoproteínas/metabolismo , Homeostase , Cálculos Renais/etiologia , Cálculos Renais/metabolismo , Mitocôndrias/metabolismo , Chaperonas Moleculares/metabolismo , Ratos
13.
Urolithiasis ; 50(4): 439-445, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35678848

RESUMO

Autosomal recessive disorders are prevalent in Pakistan, a developing South Asian country where consanguineous marriages are common. This study seeks to determine the prevalence of monogenic causes in children presenting with nephrocalcinosis and nephrolithiasis at a dialysis and transplant center in Karachi, Pakistan. A retrospective analysis was conducted in children aged 1-18 years presenting with nephrocalcinosis, between 2010 and 2019. Demographic information, clinical profile, laboratory parameters and stone analysis were collected, on a pre-designed questionnaire. One hundred and twenty-six children were included, with 11 and 3 diagnosed with renal tubular acidosis and Bartter's syndrome respectively. Next-generation sequencing and Sanger sequencing was performed on 112 children. Eighty-seven patients were diagnosed with primary hyperoxaluria, with mutations in alanine-glyoxylate-aminotransferase gene found in 73, followed by glyoxylate reductase/hydroxy-pyruvate reductase in 13, and 4-hydroxy-2-oxaloglutarate aldolase in 1. Twenty-five patients reported negative for mutations. Sixty-four percent were males, with a statistically significant difference (p < 0.05). History of parental consanguineous marriage was found in 98% of the cohort. Fifty-four and 40 patients presented to the clinic with Chronic Kidney Disease Stage 1 and Stage 5, respectively, with a statistically significant difference p = 0.007. Mutations noted in our cohort are different and more severe than those reported in the developed world. The disease poses a major disease burden in developing world context with the only treatment option of combined liver-kidney transplantation not available in Pakistan.


Assuntos
Hiperoxalúria Primária , Hiperoxalúria , Cálculos Renais , Nefrocalcinose , Criança , Efeitos Psicossociais da Doença , Feminino , Ligação Genética , Humanos , Hiperoxalúria/complicações , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/epidemiologia , Hiperoxalúria Primária/genética , Cálculos Renais/complicações , Masculino , Nefrocalcinose/epidemiologia , Nefrocalcinose/genética , Paquistão/epidemiologia , Estudos Retrospectivos
14.
Curr Opin Urol ; 32(4): 373-378, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35674681

RESUMO

PURPOSE OF REVIEW: To confirm the need for a metabolic evaluation in stone formers based on the latest information published in the last 24 months and in the current 2022 American and European urological guidelines. RECENT FINDINGS: Recent studies suggest that urolithiasis prevalence has been increasing since 1990. Along with it, metabolic abnormalities that contribute to the development of kidney stones are also increasing, such as hyperuricosuria, hyperoxaluria, hypocitraturia, hypomagnesuria, hypocalciuria, hypophosphaturia, and hyperuricemia. Those abnormalities can only be detected through a metabolic evaluation in patients with stone disease. SUMMARY: It is important for us, urologists, to have in mind the actual stone prevalence worldwide. As part of our initial evaluation of the patient with urolithiasis, we must not forget to perform the basic metabolic analysis and, according to the patient's risk classification, continue with a deep metabolic analysis. This extensive analysis includes blood and urine tests. The urinalysis covers 24-h urinalysis, and it would be accurate to also have an early fresh urine analysis. Moreover, identifying the stone type is intimately correlated with the search for other metabolic parameters.


Assuntos
Hiperoxalúria , Cálculos Renais , Urolitíase , Humanos , Cálculos Renais/diagnóstico , Cálculos Renais/epidemiologia , Cálculos Renais/etiologia , Prevalência , Fatores de Risco , Urinálise , Urolitíase/diagnóstico , Urolitíase/epidemiologia
15.
Probiotics Antimicrob Proteins ; 14(5): 854-872, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35699895

RESUMO

In the present study, we characterized the probiotic properties of two commercially available bacterial strains, Lactobacillus paragasseri UBLG-36 and Lacticaseibacillus paracasei UBLPC-87, and evaluated their ability to degrade oxalate in vitro and in a hyperoxaluria-induced nephrolithiasis rat model. UBLG-36 harboring two oxalate catabolizing genes, oxalyl coenzyme A decarboxylase (oxc) and formyl coenzyme A transferase (frc), was previously shown to degrade oxalate in vitro effectively. Here, we show that UBLPC-87, lacking both oxc and frc, could still degrade oxalate in vitro. Both these strains harbored several potential putative probiotic genes that may have conferred them the ability to survive in low pH and 0.3% bile, resist antibiotic stress, show antagonistic activity against pathogenic bacteria, and adhere to epithelial cell surfaces. We further evaluated if UBLG-36 and UBLPC-87 could degrade oxalate in vivo and prevent hyperoxaluria-induced nephrolithiasis in rats. We observed that rats treated with 4.5% sodium oxalate (NaOx) developed hyperoxaluria and renal stones. However, when pre-treated with UBLG-36 or UBLPC-87 before administering 4.5% NaOx, the rats were protected against several pathophysiological manifestations of hyperoxaluria. Compared to the hyperoxaluric rats, the probiotic pre-treated rats showed reduced urinary excretion of oxalate and urea (p < 0.05), decreased serum blood urea nitrogen and creatinine (p < 0.05), alleviated stone formation and renal histological damage, and an overall decrease in renal tissue oxalate and calcium content (p < 0.05). Taken together, both UBLG-36 and UBLPC-87 are effective oxalate catabolizing probiotics capable of preventing hyperoxaluria and alleviating renal damage associated with nephrolithiasis.


Assuntos
Hiperoxalúria , Cálculos Renais , Probióticos , Animais , Hiperoxalúria/induzido quimicamente , Hiperoxalúria/prevenção & controle , Hiperoxalúria/urina , Cálculos Renais/induzido quimicamente , Cálculos Renais/prevenção & controle , Cálculos Renais/urina , Lactobacillus/metabolismo , Ácido Oxálico/efeitos adversos , Ácido Oxálico/metabolismo , Probióticos/farmacologia , Ratos
16.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(5): 583-587, 2022 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35753728

RESUMO

We reported a case of oxalate crystal-related acute kidney injury caused by orlistat. The patient was admitted for nephrotic syndrome and acute kidney injury. The pathomorphological assessment of renal biopsy showed intratubular oxalate crystals. The patient reported that she had taken orlistat regularly to loss weight for more than a year. This patient had a habit of drinking vegetable soup and strong herbal tea daily. Orlistat, an intestinal lipase inhibitor, may cause secondary hyperoxaluria, that is, intestinal hyperoxaluria. Dietary habits could be a common precipitating factor for orlistat-relevant hyperoxaluria. It was comprehensively considered to be oxalate crystal-related acute renal injury, and the patient's renal function recovered gradually after drug withdrawal. Clinicians should pay attention to screening drug-related acute kidney injury including orlistat when observing patients with unexplained acute kidney injury, and renal biopsy should be performed if necessary. It is also important to warn people who take the orlistat for weight loss about the side effects of this drug so as to adjust the eating habits.


Assuntos
Injúria Renal Aguda , Hiperoxalúria , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/complicações , Feminino , Humanos , Hiperoxalúria/induzido quimicamente , Hiperoxalúria/complicações , Hiperoxalúria/diagnóstico , Orlistate/efeitos adversos , Oxalatos , Verduras
17.
JCI Insight ; 7(13)2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35608921

RESUMO

Nephrolithiasis is a common and recurrent disease affecting 9% of the US population. Hyperoxaluria is major risk factor for calcium oxalate kidney stones, which constitute two-thirds of all kidney stones. SLC26A3 (DRA, downregulated in adenoma) is an anion exchanger of chloride, bicarbonate, and oxalate thought to facilitate intestinal oxalate absorption, as evidenced by approximately 70% reduced urine oxalate excretion in knockout mice. We previously identified a small-molecule SLC26A3 inhibitor (DRAinh-A270) that selectively inhibited SLC26A3-mediated chloride/bicarbonate exchange (IC50 ~ 35 nM) and, as found here, oxalate/chloride exchange (IC50 ~ 60 nM). In colonic closed loops in mice, luminal DRAinh-A270 inhibited oxalate absorption by 70%. Following oral sodium oxalate loading in mice, DRAinh-A270 largely prevented the 2.5-fold increase in urine oxalate/creatinine ratio. In a mouse model of oxalate nephropathy produced by a high-oxalate low-calcium diet, vehicle-treated mice developed marked hyperoxaluria with elevated serum creatinine, renal calcium oxalate crystal deposition, and renal injury, which were largely prevented by DRAinh-A270 (10 mg/kg twice daily). DRAinh-A270 administered over 7 days to healthy mice did not show significant toxicity. Our findings support a major role of SLC26A3 in intestinal oxalate absorption and suggest the therapeutic utility of SLC26A3 inhibition for treatment of hyperoxaluria and prevention of calcium oxalate nephrolithiasis.


Assuntos
Hiperoxalúria , Cálculos Renais , Animais , Antiporters , Bicarbonatos , Oxalato de Cálcio , Cloretos/metabolismo , Hiperoxalúria/tratamento farmacológico , Hiperoxalúria/etiologia , Cálculos Renais/complicações , Cálculos Renais/tratamento farmacológico , Cálculos Renais/prevenção & controle , Camundongos , Oxalatos , Transportadores de Sulfato
18.
Medicine (Baltimore) ; 101(10): e28997, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35451393

RESUMO

RATIONALE: The Chaga mushroom (Hymenochaetaceae, Inonotus obliquus) is a fungus belonging to the Hymenochaetaceae family. It is parasitic on birch and other tree species. Chaga mushrooms are rich in various vitamins, minerals, and nutrients. Some people consider these mushrooms medicinal as they have been reported to suppress cancer progression through anti-inflammatory and antioxidant effects. However, recent studies have reported that excessive ingestion of Chaga mushrooms can cause acute oxalate nephropathy. PATIENT CONCERNS: A 69-year-old man who ingested Chaga mushroom powder (10-15 g per day) and vitamin C (500 mg per day) for the past 3 months developed acute kidney injury (AKI) with the clinical manifestations of nephrotic syndrome (NS). DIAGNOSIS: Pathological findings showed focal acute tubular injury and the deposition of calcium oxalate crystals in the tubules. Light microscopy showed interstitial fibrosis and tubular atrophy, and electron microscopy showed the effacement of the foot processes in podocytes. Based on these results, the diagnosis was acute oxalate nephropathy accompanied by minimal change disease (MCD). INTERVENTIONS: The patient's kidney function did not improve with supportive care, such as hydration and blood pressure control. Thus, we recommended hemodialysis and the administration of a high dose of steroids (intravenous hydrocortisone 500 mg twice a day for 3 days and oral prednisolone at 1 mg/kg). OUTCOMES: The patient's kidney function recovered just 1 month after the start of treatment, and the MCD was completely remitted. LESSONS: In cases of AKI with an unknown cause, it is important to closely observe the patient's medication history, and it is recommended to perform kidney biopsy. Furthermore, this study showed that active dialysis and high-dose steroid treatment can restore kidney function in patients with AKI caused by acute oxalate nephropathy with MCD.


Assuntos
Injúria Renal Aguda , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hiperoxalúria , Nefrose Lipoide , Síndrome Nefrótica , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Feminino , Humanos , Inonotus , Masculino , Nefrose Lipoide/complicações , Síndrome Nefrótica/complicações , Síndrome Nefrótica/terapia , Oxalatos/efeitos adversos , Diálise Renal/efeitos adversos , Vitaminas/efeitos adversos
19.
Nutrients ; 14(8)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35458207

RESUMO

Short gut syndrome can lead to type 3 intestinal failure, and nutrition and hydration can only be achieved with parenteral nutrition (PN). While this is a lifesaving intervention, it carries short- and long-term complications leading to complex comorbidities, including chronic kidney disease. Through a patient with devastating inflammatory bowel disease's journey, this review article illustrates the effect of short gut and PN on kidney function, focusing on secondary hyperoxaluria and acute precipitants of glomerular filtration. In extensive small bowel resections colon in continuity promotes fluid reabsorption and hydration but predisposes to hyperoxaluria and stone disease through the impaired gut permeability and fat absorption. It is fundamental, therefore, for dietary intervention to maintain nutrition and prevent clinical deterioration (i.e., sarcopenia) but also to limit the progression of renal stone disease. Adaptation of both enteral and parenteral nutrition needs to be individualised, keeping in consideration not only patient comorbidities (short gut and jejunostomy, cirrhosis secondary to PN) but also patients' wishes and lifestyle. A balanced multidisciplinary team (renal physician, gastroenterologist, dietician, clinical biochemist, pharmacist, etc.) plays a core role in managing complex patients, such as the one described in this review, to improve care and overall outcomes.


Assuntos
Hiperoxalúria , Insuficiência Intestinal , Insuficiência Renal Crônica , Síndrome do Intestino Curto , Feminino , Humanos , Hiperoxalúria/complicações , Hiperoxalúria/terapia , Masculino , Nutrição Parenteral/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Síndrome do Intestino Curto/cirurgia , Síndrome do Intestino Curto/terapia
20.
Anaerobe ; 75: 102572, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35443224

RESUMO

Recent advances in understanding the association of gut microbiota with the host have shown evidence of certain bacterial therapeutic potentiality in preventing and treating metabolic diseases. Hyperoxaluria is a severe challenge in nephrology and has led to the novel gut eubiosis as current therapy. The human gut commensal, obligate anaerobic, and intestinal oxalate-degrading strains of Oxalobacter formigenes have drawn a promising significant interest for the next-generation probiotics (NGPs). This nonpathogenic, potential probiotic, and specialist oxalotrophic properties of O. formigenes give a new hope as a live biotherapeutic agent for calcium oxalate renal therapy. Numerous satisfactory outcomes of in vitro and in vivo studies were achieved on evaluating O. formigenes functionality, but the commercial production of this bacterium is yet to be achieved. This bacterium finds diverse application in dietary and endogenous oxalate degradation and the improvement of gut health, on which we concentrated our attention in this review. The relationship between good anaerobic gut bacterial dysbiosis and renal complications is comprehensively discussed to address the need for the development probiotic formulation. However, the commercial production of this bacteria on a broad scale is complex, with numerous obstacles, mainly because they are oxygen-sensitive and difficult to culture. This review will coherently present the current and available methodologies in producing, stabilizing, and delivering these NGPs to treat calcium stones. Moreover, the study presents the extensive work and key milestones achieved in the research on O. formigenes from tale to the truth.


Assuntos
Hiperoxalúria , Probióticos , Bactérias Anaeróbias/metabolismo , Oxalato de Cálcio/metabolismo , Humanos , Hiperoxalúria/complicações , Hiperoxalúria/prevenção & controle , Oxalatos/metabolismo , Oxalobacter formigenes/metabolismo , Probióticos/uso terapêutico
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