Fanconi syndrome secondary to primary biliary cholangitis: a case report / 中华肾脏病杂志

Primary biliary cirrhosis/cholangitis is an autoimmune disease. Renal tubular acidosis is a common form in PBC cases, but Fanconi syndrome is rarely reported. The paper reported a 66-year-old female patient with fatigue, renal insufficiency and elevated bile duct enzymes. The patient presented with type 2 proximal renal tubular acidosis and complete Fanconi syndrome. Laboratory examinations showed high-titer-positive anti-mitochondrial antibodies, elevated serum IgM, and type 3 cryoglobulinemia. Renal biopsy revealed interstitial nephritis, and electron micrographs showed abnormal mitochondria in proximal tubular epithelial cells. The patient's renal function ameliorated, and acid-base imbalance and electrolyte disturbances were corrected after high-dose glucocorticoid treatment.

Enfermedad renal crónica de las comunidades agrícolas, una revisión de la literatura / Chronic Kidney Disease in Agricultural Communities, review of the literature

Resumen La enfermedad renal crónica (ERC) se define como la alteración funcional o estructural progresiva de los riñones que persiste por 3 meses o más. Esta enfermedad afecta el 10 al 15 % de la población mundial, siendo la diabetes mellitus, la hipertensión arterial, las glomerulopatías primarias y las enfermedades genéticas las etiologías más frecuentemente asociadas. Sin embargo, en los países pobres se reportan otras enfermedades causantes de la ERC; entre ellas la nefropatía mesoamericana (NM). La NM se presenta principalmente en la población masculina joven, lo cual lleva a pérdida de la vida laboral productiva. En Colombia hay una alta prevalencia de ERC con etiología no estudiada (mal llamada desconocida) y hay pocas investigaciones de la ERC en las comunidades agrícolas. Teniendo en cuenta que la población campesina de Colombia se expone a noxas climáticas y laborales similares a Mesoamérica, es posible que esta nefropatía también sea una causa de ERC en nuestra población. El presente artículo hace una revisión de la ERC de las comunidades agrícolas, con el fin de sensibilizar el personal de salud en la importancia de la búsqueda de esta enfermedad en la población vulnerable, lo cual podría impactar de una forma positiva en la salud de los agricultores y campesinos.

Summary Chronic kidney disease (CKD) is defined as an abnormality of the kidney structure or function for ≥ 3 months. This disease affects 10% to 15% of the world's population, with diabetes, arterial hypertension, primary glomerulopathies and genetic disorders being the most common etiologies associated with this disease worldwide. Nevertheless, in low-income countries, other diseases causing CKD are also reported; among them, Mesoamerican nephropathy, which is a common cause of CKD in Mesoamerica, especially in the young male population, leading to loss of productive working capacity. In Colombia, the prevalence of CKD with unknown etiology is high and there are few studies on chronic kidney disease in agricultural communities, given that the agricultural population in Colombia is exposed to harmful climatic and occupational agents similar to those in Mesoamerica, it is possible that this nephropathy is also a cause of CKD in our population. This article provides an overview of CKD in agricultural communities to sensitize health workers to the importance of screening for this disease in vulnerable populations, which could have a positive impact on the health of farmers.

Analysis of the characteristics of IgG4-related membranous nephropathy with literature review / 中华风湿病学杂志

Objective:By retrospectively analyzing 6 cases of IgG4-related membranous nephropathy (IgG4-MN), combined with literature review, to explore the clinical and renal pathological characteristics of the disease, and improve clinicians' understanding of the disease.Methods:The data of six patients with biopsy-proven IgG4-MN in the nephrology center of our hospital during April 2017 to January 2021 were collected. At the same time, we reviewed the literature systematically and summarized the clinicopathological characteristics.Results:Six male patients with the age ranged fom 55 to 75 years old were described. Urine protein level was (3.1±2.1) g/24 h, 3 cases (50%) showed nephrotic syndrome and 4 cases (67%) had elevated serum creatinine. The median creatinine level was (103±24) μmol/L. Six cases (100%) had elevated serum immunoglobulin (Ig)E level, and 4 cases (67%) had elevated IgG4. M-type phospholipase A2 receptor (PLA2R) was positive in 1 case (17%) and tubulointerstitial nephritis (TIN) was present in 6 cases. The review of the literature suggested that a total of 49 cases with IgG4-MN were reported, including 6 cases in this report. There were 40 males (40/46, 87%), with a age range of (61±12) years old, 32 cases (32/49, 65%) showed nephrotic syndrome range proteinuria, and the proportion of serum IgG and IgG4 increase was 61%(20/33) and 88% (36/41), respectively, 13 cases (13/15, 87%) had elevated serum IgE level, 47% (14/30) had low-complement C3 and 44%(12/27) had low-complement C4 level. The main organs involved were pancreas (15/37) and lymph nodes (16/37). Renal pathology showed TIN in 74%(36/49). Electron dense deposition was mainly subepithelial deposits. 7%(2/28) were positive for anti-PLA2R antibody in serum, 17%(3/18) were positive for PLA2R in kidney tissue, 6%(1/18) were suspected positive for PLA2R in kidney tissue, and 8%(1/12) were dual positive in blood and kidney tissue.Conclusion:IgG4-MN usually presents with nephrotic range proteinuria or nephrotic syndrome in middle-aged and elderly patients. Most of them are complicated with TIN and other organ involvement. A certain proportion of patients are PLA2R positive in IgG4-MN, and whether it is primary or secondary MN needs further study.

Síndrome de Reacción a drogas con Eosinofilia y Síntomas Sistémicos (DRESS) asociados a Nefritis Túbulo Intersticial Aguda en un adolescente / DRESS síndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) associated with Tubulo Interstitial Nephritis in a adolescent

Resumen El síndrome de DRESS (Reacción a drogas con eosinofilia y síntomas sistémicos) es una patología poco frecuente en Pediatría, descrita por primera vez en 1996, por Bocquet. Puede presentarse en un tiempo variable luego de exposición a algunos medicamentos, se caracteriza por fiebre, compromiso cutáneo y de órganos internos. En este caso, se presenta a un paciente de 13 años, con antecedente de uso de Trimetroprim sulfa desde hace 2 meses, con cuadro de 3 días consistente en fiebre y rash cutáneo, sin compromiso de mucosas, con respuesta no favorable al manejo con esteroide, requiriendo Inmunoglobulina IV. Semanas después del inicio de los síntomas y evolución estable presenta insuficiencia renal aguda que requirió terapia de reemplazo renal. Se descartaron otras patologías subyacentes de índole autoinmune. Hubo recuperación de azoados y normalización de los demás paraclínicos el día 40 de la enfermedad. El paciente continúa asintomático, 4 meses después, con tratamiento con esteroide oral, en descenso lento y gradual. Se debe considerar la evaluación permanente de las pruebas de función renal en los pacientes que presenten Síndrome de DRESS, por su asociación con Nefritis intersticial aguda y complicaciones relacionadas.

Abstract DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a rare pathology in Pediatrics, first described in 1996 by Bocquet. It can appear in a variable period of time after exposure to some medications, it is characterized by fever, skin involvement and internal organs. A 13-year-old patient is presented, with a history of use of Trimethoprim sulfa for two months, with a disease of three days of evolution, consisting of fever and skin rash, without mucosal involvement, with an unfavorable response to steroid management, requiring Intravenous inmunoglobulin. Weeks after the onset of symptoms and stable evolution, he presented acute renal failure that required renal replacement therapy. Other underlying autoimmune pathologies were ruled out. There was recovery of renal function test and normalization of the other paraclinical on day 40 of the disease. Patient remains asymptomatic four months later, with oral steroid treatment, in slow and gradual decline. Permanent evaluation of renal function tests should be considered in patients with DRESS syndrome, due to its association with acute tubulointerstitial nephritis and related complications.

Multiple myeloma presenting as acute tubulointerstitial nephritis

Background Acute tubulointerstitial nephritis (ATIN) is a very rare paraneoplastic manifestation in patients with multiple myeloma (MM). It is an uncommon pattern of renal disease in such patients. Case presentation We report a case of an 82-year-old male who was admitted with acute kidney injury. Renal biopsy showed typical findings of light chain-associated ATIN with scattered inflammatory cells in the interstitium and associated active tubulitis. No other common manifestations of MM were present at the time of presentation, including hypercalcemia, hyperuricemia, proteinuria, bone pain or lytic bone lesions. Subsequent immunoassays revealed significant serum lambda light chain burden and Bence Jones protein in urine. Immunofluorescence demonstrated linear tubular basement membranes with positive staining for lambda light chain (3+). Electron microscopy (EM) further showed interstitial edema and inflammation. All the aforementioned findings are consistent with ATIN and supported the diagnosis of MM. Conclusions In conclusion, light chain-associated ATIN should be considered in the differential diagnosis of acute interstitial nephritis. Henceforth, serum free light chains as well as serum and urine protein electrophoresis should be included in the workup of such patients.

Nefritis tubulointersticial aguda. Revisión bibliográfica / Acute interstitial nephritis. Literature review

RESUMEN La nefritis tubulointersticial aguda hace referencia a un tipo de daño renal que afecta principalmente el intersticio y ocasiona la lesión renal aguda, potencialmente reversible. Su curso puede ser subclínico, con deterioro progresivo hasta evolucionar hacia la insuficiencia renal crónica. La nefritis tubulointersticial aguda tiene múltiples etiologías, las más frecuentes son los medicamentos, productos herbales, las infecciones y las enfermedades autoinmunes. Las principales manifestaciones clínicas son la poliuria, polaquiuria, nocturia, dolor lumbar, microhematuria y leucocituria, aunque puede ser totalmente asintomática. El tratamiento depende de la causa de base y los esteroides juegan un papel importante cuando la condición es de origen medicamentoso o autoinmune. El pronóstico generalmente es bueno, si el problema se identifica de forma oportuna y se trata adecuadamente.

SUMMARY Acute tubulointerstitial nephritis is a kidney lesion that mainly affects the interstitium and can lead to a reversible acute kidney injury. It can progress subclinically, with progressive development towards chronic renal failure. Acute tubulointerstitial nephritis has several causes, being the most common medications, herbal products, infections and autoimmune diseases. The main clinical manifestations are polyuria, polaquiuria, nycturia, lumbar pain, microhematuria, leukocyturia, although the patients also can be completely asymptomatic. Treatment is determined by the underlying cause. Steroids play an important role when tubulointerstitial nephritis is caused by medication or autoimmune diseases. The prognosis is usually good if the problem is detected early and treated properly.

Perirenal capsule involvement in IgG4-related chronic interstitial nephritis: a case report and literature review / 中华肾脏病杂志

Objective@#To explore the clinicopathological features and the renal biopsy process of a case of IgG4-related chronic interstitial nephritis with perirenal capsule involved and review associated literature to improve the clinician's understanding for this disease and to perform a better renal biopsy.@*Methods@#The onset, diagnosis and treatment course of the disease were described and associated literature were reviewed to summary the clinicopathologic features and key points in renal biopsy.@*Results@#The data of the patient showed that the urine specific gravity was 1.011, with urine protein ± and urine sugar 3+. The concentration of hemoglobin was 53 g/L, serum creatinine was 1665 μmol/L, and IgG4 was 9.39 g/L. Computed tomography showed that both kidneys enlarged slightly with decreased density and low density shadow around the kidneys. On contrast-enhanced scan, irregular low-density enhancement areas were found in both kidneys, and the edge of the boundary was not clear. For the first renal biopsy, no renal parenchyma was found except mainly hyaline collagen fibrils. At the second time, 3 pieces of tissues were obtained, which showed chronic interstitial glomerulonephritis. The IgG4 positive plasma cells were about 60/HPF and the IgG4+/IgG+cells ratio was more than 40%. The diagnosis of IgG4-related chronic interstitial glomerulonephritis was confirmed. After corticosteroid treatment, the serum creatinine decreased to 502 μmol/L after the patient got rid of dialysis.@*Conclusions@#There are various manifestations of renal damage caused by IgG4-related disease. It is necessary to pay attention to the involvement of the perirenal capsule, and to balance the risk of bleeding and poor sampling in renal biopsy.

Clinical significance and pathological features of ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis / 中华肾脏病杂志

Objective@#To investigate the clinical significance and pathological features of lymphocytes and plasma cells infiltration and related ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis (IgG4-TIN).@*Methods@#Complete data was collected from 24 patients with IgG4-TIN confirmed by pathology in the Peking University First Hospital. The renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy examination. In addition, immunohistochemistry was used to detect the distribution of CD20+ B lymphocytes, CD3+ T lymphocytes and CD138+ plasma cells.@*Results@#A total of 24 patients were enrolled in the study, including 21 males (87.5%), 3 females (12.5%). The age was (58.0±10.8) years (38-75 years). Pathology analysis showed ectopic lymphoid-like structures were located in 16 (66.7%) cases and Russell bodies were detected in infiltrative plasma cells of 19(79.2%) cases with IgG4-TIN. Compared with cases without Russell body formation, cases with Russell body formation in renal interstitial plasma cells were more prone to show ectopic germinal center-like structure formation (P=0.001), tubular basement membrane (TBM) electron dense deposits (P=0.040) and reduced blood C3 levels (P=0.028).@*Conclusions@#Abnormal tubulointerstitial infiltration of ectopic lymphoid-like structures and plasma cells with prominent Russell body exist in IgG4-TIN patients, which suggests the persistent activation of lymphocytes and plasma cells in renal interstitium may contribute to the pathogenesis of IgG4-TIN.

The relationship between proton pump inhibitors and renal disease / Inibidores da bomba de prótons e sua relação com a doença renal

ABSTRACT Proton pump inhibitors (PPIs) bind to enzyme H+/K+-ATPase and inhibit its activity in the stomach, thus decreasing the secretion of gastric acid. PPIs may trigger acute interstitial nephritis, a potentially severe adverse event commonly associated with acute kidney injury. Studies have found that prolonged use of PPIs may increase the risk of chronic kidney disease (CKD). The increase in prescription and inadequate use of this class of medication calls for studies on the effects of prolonged PPI therapy on renal function. Therefore, this review aimed to analyze recent studies on the matter and discuss the possible consequences of the long-term use of PPIs on renal function.

RESUMO Os Inibidores da Bomba de Prótons (IBPs) são medicamentos que inibem a enzima H+/K+-ATPase no estômago, diminuindo a secreção gástrica. Esses medicamentos podem desencadear nefrite intersticial aguda, evento adverso potencialmente grave e que pode cursar com lesão renal aguda. Além disso, pesquisadores têm observado que o uso prolongado de IBPs pode também aumentar o risco de progressão da doença renal crônica (DRC). Com o crescimento da prescrição e o uso inadequado dessa classe de medicamentos, torna-se importante o estudo dos efeitos do uso prolongado dos IBPs sobre a função renal. Assim, esta revisão pretende abordar os recentes estudos sobre o tema e discutir as possíveis consequências que o uso contínuo dos inibidores da bomba de prótons pode causar na função renal.

Tubulointerstitial nephritis and uveitis syndrome in children: report of three cases / Nefrite tubulointersticial e uveíte em idade pediátrica: descrição de três doentes

ABSTRACT Tubulointerstitial nephritis and uveitis syndrome is a rare and probably underdiagnosed condition. Renal and ocular manifestations may not occur simultaneously, making the diagnosis more difficult. Nephritis may be asymptomatic; therefore, renal function evaluation is essential for diagnosis. Urinary β2-microglobulin levels may be particularly useful. Uveitis, mostly anterior, nongranulomatous and bilateral, occurs usually after the onset of nephritis. Treatment includes corticosteroids and, eventually, other immunosuppressant agents. Renal disease is usually benign and resolves spontaneously or after treatment with systemic corticosteroids. Uveitis, however, may be chronic or recurrent. The authors described the cases of three pediatric patients diagnosed with tubulointerstitial nephritis and uveitis syndrome. The goal of this paper was to warn the medical community over the need to screen patients with uveitis for renal disease.

RESUMO A síndrome nefrite tubulointersticial e uveíte é uma doença rara, provavelmente subdiagnosticada. As manifestações renais e oculares podem não ocorrer simultaneamente, tornando o diagnóstico mais difícil. A nefrite é geralmente assintomática, tornando fundamental a avaliação da função renal em doentes com uveíte. O doseamento da excreção urinária de β2-microglobulina é particularmente útil para o diagnóstico. A uveíte, tipicamente anterior, não granulomatosa e bilateral, manifesta-se após a nefrite na maioria dos casos. O tratamento inclui corticoides e, por vezes, outros imunossupressores. A doença renal tem evolução benigna, resolvendo-se espontaneamente ou com terapêutica com corticoides sistêmicos na maioria dos casos, no entanto, a uveíte pode ser crônica ou recorrente. Os autores descrevem três casos de síndrome nefrite tubulointersticial e uveíte, diagnosticados em idade pediátrica, e pretendem alertar para a necessidade de pesquisar sempre alterações renais nos doentes com uveíte.

Association of urinary kidney injury molecu le-1 with renal tubulointerstitial lesions and its clinical significance in lupus nephritis patients / 中华风湿病学杂志

Objective To explore the association of urinary level of kidney injury molecule-1 (KIM-1) with renal tubulointerstitial lesions in patients with lupus nephritis (LN). And to find a potential clinical biomarker, which could reflect the specific tubulointerstitial lesions of LN. Methods Sixty cases of biopsy proven new-onset LN patients were enrolled into the study. And 10 normal kidney tissues were collected, which came from 10 patients with kidney trauma or renal tumor nephrectomy. Sixty patients with LN were divided into mild disease group, moderate disease group, severe disease group and the extremely severe disease group according to the criteria of 2000 Hill's morphologic index for the evaluation of renal pathology. Urine and renal tissues specimen were collected. The clinical and pathological data were analyzed retrospectively. Urine level of KIM-1 was detected by enzyme linked immunosorbent assay (-). Immunohistochemical staining was used to observe the expression of KIM-1 in the renal tissue. T-test, One-Way analysis of variance(ANOVA) test or rank sum test and Pearson or Spearman correlation analysis were used for statistical analysis. Results ①With the aggravation of tubulointerstitial lesions, the urinary level of KIM-1 was increased gradually, which was shown in the control group [(0.32 ±0.03) ng/ml], mild group [(2.31 ±0.30) ng/ml], moderate group [(6.12 ±0.51) ng/ml], severe group [(12.51 ±1.83) ng/ml] and the extremely severe group [(15.30 ±2.11) ng/ml] (all P0.05). The expression of KIM-1 in the renal tissue was positively correlated with serum creatinine (SCr), quantity of 24 h UP, SLEDAI, R-SLEDAI, GAI, TLAI and AI (r=0.780, 0.780, 0.812, 0.727, 0.735, 0.910, 0.701, P0.05). Conclusion Urinary KIM-1 enables to assess the tubulointerstitial lesion in LN patients, and it can be a sensitive biomarker to predict the tubulointerstitial damage and to evaluate the degree of tubulointerstitial lesions.

Embarazo y hemodiálisis / Pregnancy and hemodialysis

Fundamento: la hemodiálisis es el método de primera elección para sustituir la función renal en mujeres con insuficiencia renal crónica o aguda durante el embarazo o posparto. Las complicaciones perinatales son frecuentes, sin embargo, el conocimiento de la adecuación de la técnica en el tratamiento médico de estas pacientes puede contribuir a la reducción de su presentación y mejorar los resultados perinatales. Objetivo: demostrar la importancia de individualizar la hemodiálisis de gestantes con insuficiencia renal aguda para preservar la vida de la madre y el feto. Caso clínico: paciente de 36 años con gestación de 31 semanas que ingresó por trombosis venosa profunda en pierna derecha y presentó insuficiencia renal aguda por nefritis intersticial aguda. La paciente requirió tratamiento de hemodiálisis durante tres semanas y logró una gestación exitosa. Resultados: se logró que la paciente llegara a las 35, 3 semanas de gestación, momento en el que se realizó la cesaria sin complicaciones para la madre ni el bebé. Conclusión: la práctica de hemodiálisis en una paciente durante el embarazo representa un reto para el equipo médico multidisciplinario ya que las complicaciones perinatales son más frecuentes. El conocimiento de los aspectos técnicos y recomendaciones médicas del tratamiento con hemodiálisis en este tipo de pacientes contribuyó al éxito del embarazo en esta gestante.

Background: hemodialysis is the first-choice method to substitute the renal function for women with chronic kidney disease or acute kidney injury during pregnancy or the postpartum period. Perinatal complications are frequent; nevertheless, knowing the adequacy of the technique in the medical treatment of these patients can contribute to reduce the presentation of the disease or improve the perinatal results. Objective: to show the importance of individualizing the hemodialysis of pregnant women with acute kidney injury to preserve the life of the mother and the fetus. Clinical case: a thirty-six-year-old female patient with 31 weeks of gestation that is admitted because of deep vein thrombosis in the right leg. The patient presented acute kidney injury caused by acute interstitial nephritis. She required hemodialysis treatment for three weeks and had a successful pregnancy. Results: the 35, 3 weeks of gestation were accomplished; a cesarean section was conducted at this time with no complications for the mother or the baby. Conclusion: conducting a hemodialysis in a pregnant woman is a challenge to the multidisciplinary medical team since perinatal complications are more frequent. To know the technical aspects and the medical recommendation for the treatment with hemodialysis for this kind of patients contributed to the success of this pregnancy.

Micosis fungoide en estadio tumoral: presentación de un caso / Mycosis fungoides in tumoral stage: a case report

Fundamento: la micosis fungoide es una neoplasia maligna originada en los linfocitos T, de curso crónico y caracterizada por lesiones que pueden ser máculas (eritematosas, hipo e hiperpigmentadas); pápulas; placas; parches, a veces poiquilodérmicos; nódulos o tumores que pueden ulcerarse y llegan ocasionalmente a la eritrodermia. Aunque es la forma más común de todos los linfomas primarios cutáneos de células T (44 %), es una enfermedad rara. Objetivo: presentar el caso clínico de un paciente con el diagnóstico de micosis fungoide. Caso clínico: paciente de 43 años de edad que desde hace tres años presenta lesiones en piel que al inicio se describieron nodulares. Estas lesiones se distribuían a nivel de genitales externos, eran eritematosas, de superficie lisa, con diámetro entre uno y dos centímetros, en número mayor de dos docenas, algunas ellas localizadas en axilas, cara, cuero cabelludo y dorso. Se encontraron además placas eritematoescamosas que presentaban bordes definidos y se distribuían de forma aislada, mientras otras confluían y formaban placas de mayor tamaño. Se realizó biopsia de las lesiones de piel con el diagnóstico de linfoma cutáneo de células T, tipo micosis fungoide en estadio tumoral. Conclusión: la micosis fungoide es una enfermedad rara, sobre todo en etapa temprana. Puede diagnosticarse erróneamente como dermatitis de contacto, psoriasis o dermatitis atópica, por lo que es importante tener en cuenta la enfermedad para su diagnóstico precoz.

Background: mycosis fungoides is a malignant neoplasm that originates in the T-cells. It has a chronic course and it is characterized by lesions that can be maculae (erythematous, hypopigmented and hyperpigmented); papulae; plaques; patches, sometimes poikilodermic; nodules or tumors that can ulcerate and get occasionally to erythroderma. Although it is the most common among cutaneous T-cell lymphomas (44 %), it is a rare disease. Objective: to present the clinical case of a patient with the diagnosis of mycosis fungoides. Clinical case: a forty-three-year-old male patient who had presented lesions in the skin for three years. Initially, the lesions were described as nodular. These lesions were distributed at the level of the external genitals, in higher number than two dozens and were erythematous, flat and one to two centimeters in diameter. Some of the lesions were in the axillae, face, scalp and dorsum. Erythematous, scaly plaques were found presenting well-defined edges. Some of the plaques were distributed isolated, while others joined to form bigger plaques. A biopsy of the skin lesions was made and proved positive for cutaneous T-cell lymphoma, type mycosis fungoides in tumoral stage. Conclusion: mycosis fungoides is a rare disease, mainly in the initial stage. It can be wrongly diagnosed as contact dermatitis, psoriasis or atopic dermatitis; that is why it is important to take into account the disease to early diagnose it.

Sustained increase of microRNA-21 abundance drives aristolochic acid-induced acute kidney injury to renal tubulointerstitial fibrosis / 中华肾脏病杂志

Objective To investigate the role of increased microRNA-21 (miR-21) in the development of renal tubulointerstitial fibrosis secondary to aristolochic acid induced acute kidney injury.Methods C57BL/6J male mice were intraperitoneally injected with aristolochic acid at a dose of 10 mg/kg.Blood samples and kidneys were harvested at day 1,3,7,14,28 after aristolochic acid treatment.To assess the role of miR-21 in aristolochic acid induced acute kidney injury to chronic kidney disease progression,mice were intravenously injected with anti-miR-21 or anti-scramble (10 mg/kg) at 1 h before aristolochic acid dosing,as well as d5 and d10 after aristolochic acid dosing.Results Increased serum creatinine and severe kidney injury were found at d3 after aristolochic acid treatment.Renal tubulointerstitial fibrosis was developed at d14 after aristolochic acid treatment.Protein expression of α-SMA,vimentin and collagen Ⅰ were significantly up-regulated at d7 and peaked at d14 (P ＜ 0.01),while protein abundance of E-Cadherin decreased at d14 and lasted until d28 (P ＜ 0.01).The abundance of miR-21 increased at d7 after aristolochic acid dosing,peaking at d14 and thereafter maintaining at a high level.Anti-miR-21 intervention relieved renal injury with reduced serum creatinine (P ＜ 0.05) and attenuation of renal tubulointerstitial fibrosis.Besides,the protein expression of α-SMA,vimentin,and collagen Ⅰ/Ⅳ was all down-regulated after anti-miR-21 treatment (P ＜ 0.05).PTEN was up-regulated and the ratio of its downstream genes p-AKT/AKT was decreased.(P ＜ 0.05) Conclusions A single high dose of aristolochic acid leads to acute kidney injury and the development of renal tubulointerstitial fibrosis secondary to AKI.Renal tubulointerstitial fibrosis could be partially reversed by inhibiting miR-21 via PTEN/p-AKT pathway.

A Case of Tubulointerstitial Nephritis and Uveitis with Fanconi Syndrome / 대한내과학회지

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease that comprises 4.7% of acute interstitial nephritis. With reno-ocular manifestations, TINU syndrome is accompanied by symptoms such as fever, fatigue, malaise, anorexia, vomiting, and arthralgia. TINU syndrome is reported mainly in children or adolescent girls, and it is rare in adults. Although TINU syndrome can present with multiple renal tubular defects, Fanconi syndrome characterized by generalized impairment of proximal tubular function, leading to renal glucosuria, hyperuricosuria, hyperphosphaturia, proximal renal tubular acidosis, and kaliuresis leading to hypokalemia, has rarely been described. We report a case of TINU syndrome with Fanconi syndrome in a 46-year-old HLA B27-positive Korean woman.

IgG4-Related Tubulointerstitial Nephritis Accompanied by Henoch-Schonlein Purpura / 대한내과학회지

Tubulointerstitial nephritis is one of the common manifestations of immunoglobulin G (IgG)4-related disease; however, among all cases of tubulointerstitial nephritis undergoing renal biopsies, IgG4-related tubulointerstitial nephritis seems to be relatively rare because of its trivial urinary findings. A previously healthy 54-year-old man was referred to our clinic with a 4-week history of lower leg purpura and renal dysfunction. A kidney biopsy was planned because of bilateral renomegaly, by imaging studies, and elevated serum creatinine levels. Pathological findings in the kidney showed prominent infiltration of IgG4-postive plasma cells in the tubulointerstitium, but not the glumeruli. A skin biopsy revealed leukocytoclastic vasculitis, accompanied by deposition of IgA and C3 in the vascular wall, indicating Henoch-Schonlein purpura (HSP). Although cases of combined IgG4-related disease and microvasculitis, including HSP, are extremely rare, the possibility of an association between two diseases deserves attention.

Correlation between urinary biomarkers and pathological lesions in drug-induced tubulointerstitial nephritis / 中华内科杂志

Objective To find some urinary biomarkers for differential diagnosis in drug-induced tubulointerstitial nephritis (DTIN) by accessing the relationship between their changes and the pathological processes of DTIN.Methods Forty patients biopsy-proven DTIN and 24 healthy controls were enrolled in this study.The urine samples of DTIN patients were collected on the day of biopsy and were measured for the following biomarkers: urinary TGF-β with enzyme-linked immunosorbent assay (ELISA);urinary IL-6 with radio-immunoassay;N-acetyl-β-D-glucosaminidase (NAG) with enzyme-substrate colorimetric assay;α1-microglobulin (α1-MG) with immune transmission turbidity method.Meanwhile, the pathological changes on renal biopsy were analyzed semi-quantitatively and scored.The relationship between these pathological changes and the urinary biomarkers were analyzed and receiver operating characteristic curve ( ROC curve) of those biomarkers in distinguishing different pathological lesions were constructed.Results Urinary α1- MG levels were positively correlated to interstitial edema, inflammatory cell infiltration and tubular atrophy, while urinary IL-6 were negatively correlated to the above parameters.Urinary NAG had positive relationship with inflammatory cell infiltration and tubular atrophy, while urinary TGF-β had positive relationship with tubular atrophy.ROC analysis results indicated that the area under curve (AUC) of α1-MG was larger than that of NAG (0.797 vs 0.734, P ＜ 0.05 ).Combined measurement of α1-MG and NAG could enhance the sensitivity of detecting interstitial inflammatory cell infiltration.For detecting interstitial edema and tubular atrophy, only α1-MG had statistical significance ( AUC = 0.723, P = 0.027;AUC = 0.774, P = 0.008,respectively).Conclusions Urinary α1-MG and NAG levels can reflect the severity of interstitial inflammatory infiltration, combined measurement of both can enhance sensitivity.Urinary α1-MG level can also reflect the degree of interstitial edema and tubular atrophy.

Characteristics of B-ultrasonic renal changes in chronic aristolochic acid nephropathy / 中华肾脏病杂志

Objective To observe the B- ultrasonic (B-US) renal changes of chronic aristolochic acid nephropathy (CAAN) patients and to determine its value in disease diagnosis. Methods The renal B-US data of 124 CAAN patients were retrospectively studied. The relationship between the B-US characteristics and the renal function was tested. Clinicopathological data of 19 CAAN patients underwent renal biopsy were compared with those of 18 patients with chronic tubulointerstitial nephropathy due to none-aristolochic acid causes (non-AAN-CTIN). Results The characteristics of renal B-US changes in CAAN patients included diminished parenchyma thickness (90.3%), atrophy of the kidney (62.90%) and asymmetrically shrinked kidneys (17.74%). The renal B-US markers, including the longitude, the volume and the parenchyma thickness, were closely associated with the level of Scr, eGFR and the function of renal tubules (P

Expression of surfactant protein A in the rat kidney with acute pyelonephritis / 中华肾脏病杂志

Objective To characterize the expression of surfactant protein A (SP-A) in normal and acute pyelonephritic rat kidneys and to study the correlation of infection and inflammation with SP-A expression. Methods Twenty-one rats were randomly assigned into three groups: control, sham operation and pyelonephritic group. HE staining was used to determine tubulointerstitial inflammation. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting were used to determine the mRNA expression and protein level of SP-A. Immunohistochemical staining was used to label the localization and intensity of SP-A expression in kidney tissue. The correlation between intensity of SP-A expression and interstitial inflammation was also evaluated. Results In pyelonephritic group, tubulointerstitial inflammation was more prominent than that in control and sham groups (54.3?11.5,6.4?1.4, 8.6?1.9,respectively). RT-PCR and Western blotting revealed that SP-A expression was up-regulated in pyelonephritic group (in mRNA level: 2.2+0.58, 0.9?0.25, 1.1? 0.30; in protein level: 0.45?0.09, 0.24?0.05, 0.26?0.05, respectively). Immunohistochemical staining demonstrated that SP-A expression was mainly localized on epithelial cells in outer medullary and collecting tubules in normal group and sham group, but strong staining extended to collecting tubules in pyelonephritic group. The tubulointerstitial inflammation score was positively correlated with the intensity of SP-A expression (r=0.67,P