Oxalate nephropathy and chronic turmeric supplementation: a case report / Nefropatia por oxalato e suplementação crônica de cúrcuma: relato de caso

ABSTRACT We present a case of a 69-year-old man who presented for routine check-up and was incidentally found to have kidney failure with an initially unrevealing history and bland urinary sediment. He was diagnosed with oxalate nephropathy in the setting of chronic turmeric supplementation and chronic antibiotic therapy with associated diarrhea. Our case provides several key insights into oxalate nephropathy. First, the diagnosis requires a high index of clinical suspicion. It is uncommonly suspected clinically unless there is an obvious clue in the history such as Roux-en-Y gastric bypass or ethylene glycol poisoning. Diagnosis can be confirmed by histopathologic findings and corroborated by serum levels of oxalate and 24-hour urinary excretion. Second, the diagnosis can often be missed by the pathologist because of the characteristics of the crystals unless the renal pathologist has made it a rule to examine routinely all H&E sections under polarized light. This must be done on H&E, as the other stains dissolve the crystals. Third, one oxalate crystal in a routine needle biopsy is considered pathologic and potentially contributing to the AKI or to the CKD in an important way. Fourth, secondary oxalosis can be largely mitigated or prevented in many cases, especially iatrogenic cases. This can come through the surgeon or the gastroenterologist providing proper instructions to patients on an oxalate-restricted diet or other specific dietary measures. Lastly, this case highlights the success that results from cooperation and communication between the pathologist and the treating physician.

RESUMO Relatamos o caso de um homem de 69 anos que se apresentou para exame de rotina e descobriu-se incidentalmente que ele tinha insuficiência renal, com histórico inicialmente não revelador e sedimento urinário brando. Ele foi diagnosticado com nefropatia por oxalato no contexto de suplementação crônica de cúrcuma e antibioticoterapia crônica com diarreia associada. Nosso caso fornece diversas sugestões importantes sobre nefropatia por oxalato. Primeiro, o diagnóstico requer elevado índice de suspeita clínica. A suspeita clínica é incomum, a menos que haja evidência óbvia no histórico, como bypass gástrico em Y de Roux ou envenenamento por etilenoglicol. O diagnóstico pode ser confirmado por achados histopatológicos e corroborado por níveis séricos de oxalato e excreção urinária de 24 horas. Segundo, o diagnóstico pode passar despercebido pelo patologista devido às características dos cristais, a menos que o patologista renal estabeleça como regra examinar rotineiramente todas as seções coradas com H&E sob luz polarizada. Isso deve ser feito com H&E, pois, outras colorações dissolvem os cristais. Em terceiro lugar, um cristal de oxalato em biópsia por agulha de rotina é considerado patológico, contribuindo potencialmente para LRA ou para DRC de maneira significativa. Em quarto lugar, a oxalose secundária pode ser amplamente mitigada ou prevenida em muitos casos, especialmente casos iatrogênicos. Isso pode ser feito pelo cirurgião ou pelo gastroenterologista, fornecendo instruções adequadas aos pacientes sobre uma dieta restrita em oxalato ou outras medidas dietéticas específicas. Por fim, esse caso destaca o sucesso que resulta da cooperação e comunicação entre o patologista e o médico assistente.

Improvement of Na+-K+ ATPase Activity and Gene Expression Associated with Glomerular Ultrastructural Protection in Diabetic Nephropathy by Acacia senegal: Role of Oxidative Stress Disturbances / Mejora de la actividad Na+-K+ ATPasa y la Expresión Génica Asociada con la Protección Ultraestructural Glomerular en la Nefropatía Diabética por Acacia senegal: Papel de las Alteraciones del Estrés Oxidativo

SUMMARY: This study assessed the effects of Acacia Senegal (AS) combined with insulin on Na+/K+-ATPase (NKA) activity and mRNA expression, serum glucose, renal function, and oxidative stress in a rat model of diabetic nephropathy (DN). Sixty rats were equally divided into six groups: normal control, normal+AS, diabetic (DM), DM+insulin, DM+AS, and DM+insulin+AS groups. Diabetes mellitus (type 1) was induced by a single injection of streptozotocin (65 mg/kg), and insulin and AS treatments were carried until rats were culled at the end of week 12. Serum glucose and creatinine levels, hemoglobin A1c (HbA1c) were measured. Renal homogenate levels of NKA activity and gene expression, malondialdehyde, superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were evaluated as well as kidney tissue histology and ultrastructure. Diabetes caused glomerular damage and modulation of blood and tissue levels of creatinine, glucose, HbA1c, malondialdehyde, NKA activity and gene expression, SOD, catalase and GSH, which were significantly (p<0.05) treated with AS, insulin, and insulin plus AS. However, AS+insulin treatments were more effective. In conclusion, combined administration of AS with insulin to rats with DN decreased NKA activity and gene expression as well as oxidative stress, and improved glycemic state and renal structure and function.

Este estudio evaluó los efectos de Acacia senegal (AS) combinada con insulina sobre la actividad Na+/K+- ATPasa (NKA) y la expresión de ARNm, la glucosa sérica, la función renal y el estrés oxidativo en un modelo de nefropatía diabética (ND) en ratas. Sesenta ratas se dividieron equitativamente en seis grupos: control normal, normal+AS, diabética (DM), DM+insulina, DM+AS y DM+insulina+AS. La diabetes mellitus (tipo 1) se indujo mediante una única inyección de estreptozotocina (65 mg/kg), y los tratamientos con insulina y AS se llevaron a cabo hasta que las ratas fueron sacrificadas al final de la semana 12. Se midieron niveles séricos de glucosa y creatinina, hemoglobina A1c (HbA1c). Se evaluaron los niveles de homogeneizado renal de actividad NKA y expresión génica, malondialdehído, superóxido dismutasa (SOD), catalasa y glutatión reducido (GSH), así como la histología y ultraestructura del tejido renal. La diabetes causó daño glomerular y modulación de los niveles sanguíneos y tisulares de creatinina, glucosa, HbA1c, malondialdehído, actividad y expresión génica de NKA, SOD, catalasa y GSH, los cuales fueron tratados significativamente (p<0,05) con AS, insulina e insulina más AS. Sin embargo, los tratamientos con AS+insulina fueron más efectivos. En conclusión, la administración combinada de AS con insulina a ratas con DN disminuyó la actividad de NKA y la expresión genética, así como el estrés oxidativo, y mejoró el estado glucémico y la estructura y función renal.

Diplejía facial en paciente con nefropatía por virus de inmunodeficiencia humana

Introducción: El síndrome de Guillain-Barré comprende un grupo heterogéneo de polirradiculoneuropatías inflamatorias agudas autoinmunes, las cuales se caracterizan por debilidad simétrica de extremidades con pérdida de reflejos miotáticos. Presenta gran variabilidad clínica, donde la afectación facial es habitual, sin embargo, incluye manifestaciones atípicas que dificultan el diagnóstico temprano de la enfermedad. Objetivo: Describir el comportamiento de un caso atípico de diplejía facial en un paciente con nefropatía por virus de inmunodeficiencia humana. Caso clínico: Se presentó el caso de un paciente portador de nefropatía por virus de la inmunodeficiencia humana, que comenzó con parálisis facial bilateral, como forma de presentación atípica de este síndrome. Acudió a los servicios de salud refiriendo decaimiento marcado, náuseas, vómitos, hipo y dos deposiciones líquidas. Se realizaron estudios que corroboran el diagnóstico. El tratamiento empleado facilitó la recuperación paulatina de la afección. Conclusiones: El diagnóstico precoz de las variantes atípicas de presentación del síndrome, permite un tratamiento oportuno, donde las posibilidades de complicaciones en el paciente son reducidas, así como la mortalidad asociada a la enfermedad.

Introduction: Guillain-Barré Syndrome comprises a heterogeneous group of autoimmune acute inflammatory polyradiculoneuropathies, which are characterized by symmetrical limb weakness with loss of stretch reflexes. It presents great clinical variability, where facial involvement is common; however, it includes atypical manifestations that make early diagnosis of the disease difficult. Objective: To describe the behavior of an atypical case of facial displejía in a patient with nephropathy due to Human Immunodeficiency Virus. Case report: A case of a patient with HIV nephropathy is presented, which begins with bilateral facial paralysis, as an atypical presentation of this syndrome. The patient went to the health services reporting marked weakness, nausea, vomiting, hiccups and two liquid stools. Studies were performed that corroborate the diagnosis. The treatment used facilitated the gradual recovery of the condition. Conclusions: Early diagnosis of the atypical presentation variants of the syndrome allows timely treatment, where the chances of complications in the patient are reduced, as well as the mortality associated with the disease.

Dendrobii Caulis Mixture-containing Serum Protects Mice from Podocyte Injury Induced by High Glucose / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Dendrobium mixture （DMix）-containing serum on high glucose-induced podocyte injury in mice. MethodThe MPC5 mouse glomerular podocytes were cultured in vitro， and the optimal glucose concentration for modeling， modeling time， and concentration of DMix-containing serum for administration were determined. The cells were classified into normal （5.5 mmol·L-1 glucose+10% blank serum）， model （30 mmol·L-1 glucose+10% blank serum）， DMix-containing serum （30 mmol·L-1 glucose+10% DMix-containing serum）， ferroptosis inhibitor （Fer-1， 30 mmol·L-1 glucose+10% blank serum+1 μmol·L-1 Fer-1） groups. The corresponding kits were used to measure the levels of Fe2+ and lactate dehydrogenase （LDH） in cells. Enzyme-linked immunosorbent assay was employed to determine the content of glutathione （GSH） and lipid peroxide （LPO） in cells. Fluorescence probe was used to measure the reactive oxygen species （ROS） level. Real-time fluorescence quantitative polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Wilms' tumor-1 （WT-1）， desmin， long chain acyl-CoA synthase 4 （ACSL4）， and glutathione peroxidase 4 （GPX4） in podocytes. ResultCompared with the blank group， the intervention with 30 mmol·L-1 glucose for 48 h reduced podocyte viability （P<0.01）， and the 10% DMix-containing serum showed the most significant improvement in podocyte viability （P<0.01）. Compared with the normal group， the model group presented elevated levels of Fe2+， LDH， LPO， and ROS， lowered GSH level， up-regulated mRNA and protein levels of desmin and ACSL4， and down-regulated mRNA and protein levels of WT-1 and GPX4 （P<0.01）. Compared with the model group， the DMix-containing serum lowered the Fe2+， LDH， LPO， and ROS levels， elevated the GSH level， down-regulated the mRNA and protein levels of desmin and ACSL4， and up-regulated the mRNA and protein levels of WT-1 and GPX4 in podocytes （P<0.05， P<0.01）. ConclusionDMix-containing serum exerts a protective effect on high glucose-induced podocyte injury by inhibiting ferroptosis.

Inhibitory effects of Ginkgo biloba extract on renal inflammation in diabetic nephropathy model mice and its mechanism / 中国药房

OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract （GBE） on renal inflammation in diabetic nephropathy （DN） model mice， and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group， positive control group [metformin 200 mg/（kg·d）]， GBE low-dose and high-dose groups [100， 200 mg/（kg·d）]， with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically， control group and model group were given constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The body weight， fasting blood glucose， 24-hour food intake， 24-hour urine output， monocyte chemoattractant protein-1 （MCP-1）， interleukin-12 （IL-12）， IL-10， advanced glycation end products （AGEs）， blood urea nitrogen （BUN） and serum creatinine （Scr） of mice were measured， and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed， and the expressions of macrophage polarization marker proteins [type M1： inducible nitric oxide synthase （iNOS）； type M2： arginase-1 （Arg-1）] and AGEs-the receptor of advanced glycation end products （RAGE）/Ras homolog gene pharm_chenjing@163.com family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group， the symptoms such as renal cortical hyperplasia， vacuoles， infiltration of inflammatory cells， and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups； body weight， serum level of IL-10， the expression of Arg-1 in the renal cortex were significantly higher than model group （P＜ 0.01）； fasting blood glucose， 24-hour food intake， 24-hour urine output， serum levels of MCP-1， IL-12， BUN， Scr and AGEs， the ratio of bilateral kidneys to body weight， renal injury score， the proportion of renal interstitial fibrosis， the protein expressions of iNOS， RAGE， RhoA and ROCK1 （except for GBE low-dose group） in renal cortex were significantly lower than model group （P＜0.01）. CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice， the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.

Analysis of 111 cases of aristolochic acids nephropathy / 药学实践杂志

Objective To analyze the clinical characteristics and regularity of aristolochic acid nephropathy (AAN) induced by drugs containing aristolochic acid. Methods The clinical data of 111 patients with AAN induced by aristolochic acid were reviewed. The clinical features, medication and treatment of AAN were analyzed. Results Among 111 patients, there were more females than males (2.58∶1), 101 cases (90.99%) were over 50 years old； the mean age was (63.70±11.67) years old;the average duration of medication was (8.08±6.94) years. The drugs involved were Guanxinsuhe pill and Longdanxiegan pill in 106 cases (95.50%). Serum creatinine increased in 108 cases, urea nitrogen increased in 106 cases and hemoglobin decreased in 103 cases, most of which were hypogravity urine, mild to moderate proteinuria and occult blood. Ultrasonic examination revealed that the kidneys were damaged to varying degrees. Pathological biopsy of kidney showed renal tubular damage. Most patients had an insidious onset and varying degrees of progression, which were not proportional to the age and the duration of taking the medicine. In clinical, the renal function was progressively damaged, most of which were irreversible and with a poor prognosis. Conclusion Patients with renal impairment differed greatly individually, and the renal damage was not paralleled with the medication duration and dose of drugs containing aristolochic acid.AAN progressed rapidly, and the disease still progressed even after stopping taking drugs containing aristolochic acid. Strengthening pharmacovigilance, implementing early diagnosis and effective intervention could help to reduce the occurrence of AAN and attenuate its development.

TCM Treatment of Podocyte Injury in IgA Nephropathy Based on Multiple TCM Theories： A Review / 中国实验方剂学杂志

IgA nephropathy is the most common primary glomerular disease in China. Its clinical manifestations are mainly proteinuria， hematuria， hypertension， edema， hyperuricemia， etc. Most patients have hidden onset. 30%-40% of patients develop into end stage renal disease 10-20 years after diagnosis and rely on dialysis or kidney transplantation to maintain their lives， which is extremely harmful. Proteinuria is a common clinical manifestation of this disease， and most patients have small-to-moderate amounts of proteinuria， while 10%-24% of patients have large amounts of proteinuria. Proteinuria is the main risk factor affecting the progression of renal function in IgA nephropathy. Podocytes are the terminal part of the glomerular filtration barrier， and various factors can affect the fusion and detachment of podocyte processes that occur after podocyte injury. They are common histological lesions in IgA nephropathy and are key factors leading to proteinuria and the continuous progression of the disease. At present， Western medicine lacks targeted treatment for podocyte injury， with limited intervention methods. Drugs such as glucocorticoids are often used for treatment， and there are many adverse reactions. Based on the physiological function of podocytes， pathological and physiological changes after injury， and histological morphology of this disease， it is believed that it is closely related to traditional Chinese medicine's "Xuanfu Theory" "Kidney Collateral Syndrome" "Collateral Disease Theory"， and "Dry Blood Theory". More and more studies have shown that traditional Chinese medicine， which has the characteristics of multiple links， pathways， and targets， has a significant therapeutic effect on podocyte injury in IgA nephropathy. It can protect podocytes and reduce proteinuria and has good application and research prospects. This article systematically summarizes the mechanism and morphological changes of podocyte injury in IgA nephropathy， the understanding of podocyte injury in traditional Chinese medicine theory， and the research progress in traditional Chinese medicine treatment of podocyte injury in IgA nephropathy， so as to provide a reference for further research and application of traditional Chinese medicine intervention in podocyte injury in IgA nephropathy.

Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy / 中国药房

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

Hipopotasemia no medicamentosa como biomarcador de nefropatía crónica temprana en adultos del sur de Honduras

Introducción: La hipopotasemia es un trastorno hidroelectrolítico frecuente, asociado a enfermedades sistémicas y multifactoriales, cuya forma aguda puede complicarse y causar la muerte, pero en su presentación crónica puede ser un marcador de nefropatía. Objetivo: Caracterizar el perfil del paciente con hipopotasemia no medicamentosa atendidos de emergencia. Métodos: Se revisaron los registros de pacientes mayores de 18 años con diagnóstico de hipopotasemia, ingresados en el hospital en el período de junio 2018 a diciembre de 2019. Se colectaron datos demográficos, antecedentes médicos y evolución postratamiento. Se comparó con 108 pacientes sin hipopotasemia atendidos en el período de estudio. Resultados: Se encontraron 87 casos con edad media de 38,5 años. El 90,8 % eran hombres menores de 50 años, de oficio agricultor (29,9 %), con historia de exposición a plaguicidas y a altas temperaturas ambientales. La mayoría de ellos no tenía historia de enfermedad cardiometabólicas o renal previa. El 48,3 % de todos los pacientes con hipopotasemia (n = 42) tenía creatinina mayor a 1,2 mg/dL y 63 % tenía hiponatremia. La hipopotasemia fue moderada en 39 % y severa en 12 %, los hombres 4,7 veces más afectados que las mujeres. Respecto al grupo sin hipopotasemia y creatinina anormal, tenían mayor frecuencia de enfermedad crónica (92,5 % versus 8 %). Conclusiones: Se encontró hipopotasemia no medicamentosa en varones agricultores, sin enfermedad crónica, pero con datos de nefropatía temprana e hiponatremia, se sugirió la posibilidad de nefropatía mesoamericana. Debe establecerse una alerta epidemiológica regional y un programa de prevención y control.

Introduction: Hypokalemia is a frequent hydroelectrolytic disorder, associated with systemic and multifactorial diseases, whose acute form can be complicated and cause death, but in its chronic presentation it can be a marker of nephropathy. Objective: To characterize the profile of the patient with non-drug hypokalemia seen in an emergency. Methods: The records of patients older than 18 years diagnosed with hypokalemia, admitted to the hospital from June 2018 to December 2019, were reviewed. Demographic data, medical history, and post-treatment evolution were collected. It was compared with 108 patients without hypokalemia seen in the same period. Results: 87 cases with mean age of 38.5 years were studied. 90.8% were men under 50 years of age, who worked as farmers (29.9%), with history of exposure to pesticides and high ambient temperatures. Most of them had no history of previous cardiometabolic or renal disease. 48.3% of all patients with hypokalemia (n = 42) had creatinine higher than 1.2 mg/dL and 63% had hyponatremia. Hypokalemia was moderate in 39% and severe in 12%, and it was found that men were affected 4.7 times more than women. Regarding the group without hypokalemia and abnormal creatinine, they had higher frequency of chronic disease (92.5% versus 8%). Conclusions: Non-drug hypokalemia was found in male farmers, without chronic disease, but with evidence of early nephropathy and hyponatremia. The possibility of Mesoamerican nephropathy was suggested. A regional epidemiological alert and a prevention and control program should be established.

Utility of serum anti-phospholipase A2 receptor antibody as a biomarker in membranous nephropathy: An experience from a tertiary care center of Eastern India

Background: Membranous nephropathy (MN) is a pattern of glomerular injury. Exact categorization into primary membranous nephropathy (PMN) or secondary membranous nephropathy (SMN) is essential for treatment. An endogenous podocyte antigen, M-type phospholipase A2 receptor (PLA2R) has been discovered to be involved in the pathogenesis of PMN. Aims and Objectives: In this article, we aimed to analyze renal tissue PLA2R and serum anti-PLA2R antibodies in MN cases and determined the diagnostic utility. Materials and Methods: The study was of prospective type carried out from March 2019 to August 2020. Analysis of cases of MN was performed with PLA2R paraffin immunoflourescence and serum anti-PLA2R antibody ELISA. Results: Overall sensitivity, specificity, PPV, and NPV of serum anti-PLA2R ELISA for PMN was 91.3%, 80%, 75%, and 93.3%, respectively, and of tissue PLA2R staining for PMN was 91.67%, 81.08%, 75.86%, and 93.75%, respectively. There was strong concordance between two methods. In the patients that were followed up, we found baseline serum anti-PLA2R antibody was less in complete remission group than that in non-remission group and the reduction in serum anti-PLA2R antibody was more in complete remission group than that in non-remission group. Conclusion: Routine light and immunofluorescence examination are incapable of giving exact categorical opinion regarding PMN and SMN. Serum anti-PLA2R antibody detection and renal tissue PLA2R analysis are sensitive and specific in detecting PMN. Baseline serum anti-PLA2R antibody and anti-PLA2R antibody quantification trends are related to prognosis of PMN. So they can be incorporated as additional biomarker.

Renal biopsy in diabetic patients: clinical indicators and pathological findings / Biopsia renal en pacientes diabéticos: indicadores clínicos y hallazgos patológicos

ABSTRACT Background: In addition to diabetic nephropathies (DNP), prevalence of nondiabetic nephropathies (NDNP) is also known to be frequent in patients diagnosed with type 2 Diabetes mellitus (DM). Early diagnosis of these conditions is important for the treatment and prognosis of these patients. Aim: This study aimed to investigate the relationships between clinical and laboratory findings of type 2 diabetic patients' renal biopsies. Material and Methods: We retrospectively reviewed the medical records of 140 patients who had diagnosis of type 2 DM and underwent renal biopsy from July 2020- August 2022 at nephrology clinics of Hospital Umraniye. Renal biopsy results, presence of hypertension, diabetic retinopathy, hematuria, proteinuria; duration of the disease, biopsy indications, glycated hemoglobin (HbA1c), serum creatinine, blood urea nitrogen, albumin, and proteinuria levels in 24h urine were measured. The statistical significance level was determined as p<0,05. Results: NDNP were detected in 43,7% of the patients. Among these the most common diagnosis was interstitial nephritis (20%). The most common biopsy indication was found to be nephrotic range proteinuria (30,7%). The difference between the DNP and NDNP patients' renal biopsy indications was statistically significant (p<0,001). DNP patients had a higher retinopathy incidence (60%,11%, p<0,001). A statistically significant difference was detected between the disease duration of DNP and NDNP groups (11,23 +5,74 years, p:0,002). According to multivariate regression analysis DR and HbA1c value, more than 7% have 4, 482 and 4,591-fold increased the risk of DNP incidence (p=0,021, p:0,024). Conclusion: Early diagnosis of DNP and NDNP of diabetic patients by performing renal biopsies affects the treatment and prognosis of the patients. Therefore, when evaluating diabetic patients, its necessary not to overlook the findings suggestive of NDNP.

RESUMEN Antecedentes: Además de las nefropatías diabéticas (DNP), también se conoce la prevalencia frecuente de nefropatías no diabéticas (NDNP) en pacientes diagnosticados con Diabetes mellitus tipo 2 (DM). El diagnóstico precoz de estas condiciones es importante para el tratamiento y pronóstico de estos pacientes. Objetivo: Este estudio tuvo como objetivo investigar las relaciones entre los hallazgos clínicos y de laboratorio de las biopsias renales de pacientes diabéticos tipo 2. Material y Métodos: Revisamos retrospectivamente las historias clínicas de 140 pacientes que tenían diagnóstico de DM tipo 2, desde julio de 2020 hasta agosto de 2022, y se les realizó biopsia renal en las clínicas de nefrología del Hospital Umraniye. Se revisaron los resultados de biopsia renal, presencia de hipertensión arterial, retinopatía diabética, hematuria y proteinuria así como también la duración de la enfermedad, las indicaciones de la biopsia, la hemoglobina glucosilada (HbA1c), la creatinina sérica, el nitrógeno ureico en sangre, la albúmina y los niveles de proteinuria en orina de 24 h. El nivel de significación estadística se determinó como p<0,05. Resultados: se detectaron NDNP en el 43,7% de los pacientes. Entre estos, el diagnóstico más común fue la nefritis intersticial (20%). La indicación de biopsia más frecuente resultó ser la proteinuria en rango nefrótico (30,7%). La diferencia entre las indicaciones de biopsia renal de los pacientes DNP y NDNP fue estadísticamente significativa (p<0,001). Los pacientes con DNP tuvieron una mayor incidencia de retinopatía (60%, 11%, p<0,001). Se detectó una diferencia estadísticamente significativa entre la duración de la enfermedad de los grupos DNP y NDNP (11,23 +5,74 años, p:0,002). De acuerdo con el análisis de regresión multivariado, la presencia de DR y el valor de HbA1c en más del 7% tienen 4,482 y 4,591 veces mayor riesgo de incidencia de DNP (p = 0,021, p: 0,024). Conclusión: El diagnóstico precoz de DNP y NDNP de pacientes diabéticos mediante la realización de biopsias renales afecta el tratamiento y pronóstico de los pacientes. Por lo tanto, al evaluar pacientes diabéticos, es necesario no pasar por alto los hallazgos sugestivos de NDNP.

Crescentic IgA nephropathy following SARS-CoV-2 vaccination. Report of a case / Nefropatía por IgA extracapilar luego de la vacunación contra el SARS-CoV-2. Reporte de un caso

ABSTRACT Introduction: Studies have shown that the frequency of acute kidney injury (AKI) increases in patients with COVID-19. Acute tubular necrosis has been reported to be the most common damage in these patients, probably due to impaired renal perfusion. On the other hand, different complex pathophysiological processes may be involved due to viral infection's direct effects on the renin-angiotensin-aldosterone system, the activation of coagulopathy, the cytokine storm, and the activation of the immune system. Many glomerular diseases may be seen in these patients, like anca-associated vasculitis, membranous glomerulonephritis, and IgA nephropathy. Clinical case: We present a newly diagnosed crescentic IgA nephropathy (IgAN) case after a SARS-CoV-2 infection and vaccination. A 31-year-old man with no medical history presented with gross hematuria 24 hours after SARS-CoV-2 infection. Hematuria regressed spontaneously within three days. He was vaccinated with two doses of CoronaVac (Sinovac) three months after he had been infected by SARS-CoV-2. Then he was vaccinated with the Pfizer-BioNTech COVID-19 vaccine one month after the second dose of CoronaVac (Sinovac) vaccine. He presented with gross hematuria and subnephrotic proteinuria 24 hours after the first dose of the Pfizer-BioNTech COVID-19 vaccine. A kidney biopsy was performed and showed crescentic IgA nephropathy (IgAN). He was started on methylprednisolone and angiotensin receptor blocker. Patients who receive mRNA-based vaccines demonstrate robust antibody production against the receptor-binding domain (RBD) of the S1 protein. Similar to natural infection, due to the intense stimulation of immune response from mRNA-based vaccines compared to other vaccines, the patients may produce de novo antibodies, leading to IgA-containing immune-complex deposits. Conclusions: This case highlights the immunological effects of the novel mRNA-based SARS-CoV-2 vaccines. Nephrologists should be aware of new-onset hematuria or proteinuria after SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccine.

RESUMEN Introducción: Los estudios han demostrado que la frecuencia de insuficiencia renal aguda (IRA) aumenta en pacientes con COVID-19. Se ha informado que la necrosis tubular aguda es el daño más común en estos pacientes, probablemente debido a la alteración de la perfusión renal. Por otro lado, pueden estar involucrados diferentes procesos fisiopatológicos complejos, debido a los efectos directos de la infección viral sobre el sistema renina-angiotensina-aldosterona, la activación de la coagulopatía, la tormenta de citoquinas y la activación del sistema inmunológico. En estos pacientes se pueden observar muchas enfermedades glomerulares, como vasculitis asociada a anca, glomerulonefritis membranosa y nefropatía por IgA. Caso clínico: Presentamos un caso de nefropatía IgA extracapilar (NIgA) de nuevo diagnóstico tras una infección por SARS-CoV-2 y vacunación. Un hombre de 31 años sin antecedentes médicos presentó hematuria macroscópica 24 horas después de la infección por SARS-CoV-2. La hematuria remitió espontáneamente en 3 días. Fue vacunado con dos dosis de CoronaVac (Sinovac) tres meses después de haber sido infectado por el SARS-CoV-2. Luego fue vacunado con la vacuna Pfizer-BioNTech COVID-19, un mes después de la segunda dosis de la vacuna CoronaVac (Sinovac). Presentó hematuria macroscópica y proteinuria no nefrótica 24 horas después de la primera dosis de la vacuna Pfizer-BioNTech COVID-19. Se realizó una biopsia renal que mostró NIgA extracapilar. Comenzó con metilprednisolona y bloqueador del receptor de angiotensina. Los pacientes que reciben vacunas basadas en ARNm demuestran anticuerpos contra el dominio de unión al receptor (RBD) de la proteína S1. De manera similar a la infección natural, debido a la fuerte estimulación de la respuesta inmunitaria de las vacunas basadas en ARNm en comparación con otras vacunas, los pacientes pueden producir anticuerpos de novo, lo que lleva a depósitos de complejos inmunitarios que contienen IgA. Conclusiones: Este caso destaca los efectos inmunológicos de las nuevas vacunas contra el SARS-CoV-2 basadas en ARNm. Los nefrólogos deben estar al tanto de la aparición de hematuria o proteinuria luego de la infección por SARS-CoV-2 o la vacuna contra el SARS CoV-2 basada en ARNm.

Pathological changes in Kidney Autopsies from North Maharashtra –A Descriptive Study

Background: Chronic Kidney disease is a major public health concern. In India, the burden of chronic Kidney disease cannot be assessed properly. In such case autopsy study becomes an indispensible part of Medicine. Aim: To explore the spectrum of changes seen in kidneys and correla?ng it with clinical findings. Material & Methods: A descrip?ve study of kidneys of Medico legal autopsies from January 2019 – December 2019 was conducted. A total of 665 Medico legal autopsies were received, in 73 cases kidneys were not received, while 23 kidneys had autoly?c change. A total of 569 Kidneys were included in the study. The Gross and Microscopic features along with special stains were studied and the cause of death was noted. Results: A total of 569 kidney autopsies were assessed. On Gross 26% were congested, 13% had contracted granular kidney. On Histopathological examina?on, Non specific changes were seen in 53.4%, specific nephropathological lesions noted were chronic pyelonephri?s (8.9%), acute tubular necrosis (5.6%), sickle cell nephropathy (4.7%), tubercular nephri?s (1.2%). Conclusion: Infec?ve e?ology was the commonest cause, along with sickle cell nephropathy. It has provided the spectrum of lesions seen in this area along with correla?on of cause of death. Screening for diabetes mellitus and hypertension would lead to early detec?on and ?mely management which would reduce chronic kidney diseases.

The role of pro-inflammatory cytokines – tumor necrosis factor-alpha and interleukin 6 – in the evolution of diabetic nephropathy: A comparative study

Background: Diabetes is highly prevalent and it is responsible for the increased financial burden on healthcare. Type II diabetes is a more prevalent form of diabetes. Uncontrolled and unsupervised type II diabetes may lead to various microvascular and macrovascular complications which are responsible for high morbidity and mortality. Diabetic nephropathy (DN) is a common complication characterized by the expansion of mesangial cells with thickening of the basement and nodular glomerulosis. TNF-alpha and IL-6 play an important role in causing detrimental changes leading to nephropathy. The study of the role of these inflammatory cytokines in patients with DN may help in the early diagnosis and management. Aims and Objectives: The objectives of this study were to compare the levels of proinflammatory cytokines, TNF-?, and IL-6 in the evolution of DN patients. Materials and Methods: The present study was conducted in the Department of Biochemistry, in collaboration with the Department of Medicine (Nephrology unit); Pt. B.D. Sharma, Post Graduate Institute of Medical Sciences, Rohtak after ethical clearance. Forty patients with DN (Stages 3, 4, and 5) and forty patients with diabetes mellitus without nephropathy were taken up for study after taking informed consent. Results: The mean serum TNF-? levels in cases was 33.05 ± 29.22 pg/mL and in controls was 17.67 ± 12.33 pg/mL. On the basis of unpaired t-test, the difference between the groups was statistically highly significant (P < 0.05). The mean serum interleukin-6 levels in cases was 24.92 ± 30.16 pg/mL (2.95–155.55 pg/mL) and in controls was 6.76 ± 5.82 pg/mL (2.22–35.42 pg/mL). On the basis of the t-test, the difference between the groups was statistically highly significant (P < 0.05). Conclusion: TNF-? and IL-6 may serve as potential biomarkers for patients with DN and also in the development of newer therapeutic modalities for the prevention and treatment of DN.

Nefropatía por IgA en una adolescente con lupus eritematoso sistémico juvenil. Reporte de caso

Introducción: El lupus eritematoso sistémico juvenil (LESJ) es una enfermedad autoinmunitaria, multisistémica, caracterizada por la producción de autoanticuerpos y el desarrollo frecuente de glomerulonefritis mediada por inmunocomplejos. La nefritis lúpica es una complicación frecuente y grave del LESJ, con alta morbilidad, siendo causa de insuficiencia renal terminal en muchos de estos pacientes. La nefropatía por IgA representa la etiología más común en la población general y raramente se asocia con LESJ. Caso clínico: adolescente femenino con LESJ en quien se diagnosticó nefritis no lúpica (nefropatía por IgA). Conclusiones: El diagnóstico anatomopatológico es clave para establecer el pronóstico y planificar el tratamiento.

Introduction: Juvenile systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease characterized by the production of autoantibodies and the frequent development of immune complex-mediated glomerulonephritis. Lupus nephritis is a frequent and serious complication of JSLE, has a high associated morbidity rate, and is the cause of end-stage renal failure in many of these patients. IgA Nephropathy represents the most common etiology in the general population and is rarely associated with JSLE. Clinical case: a female adolescent with JSLE who was diagnosed with non-lupus nephritis (IgA nephropathy). Conclusions: The anatomopathological diagnosis is key to establish the prognosis and plan the treatment.

Hypomagnesemia � An overlooked parameter in type 2 diabetes mellitus

Background: Diabetes Mellitus refers to a group of common metabolic disorders that share the phenotype of Hyperglycemia. It is the leading cause of morbidity and mortality throughout the world with an estimated worldwide prevalence of 439 million by 2030 and 19% of world抯 DM patients are Indians. Magnesium is an important co-factor for various enzymes involved in Insulin secretion and is involved in sodium-potassium ATPase pump. 25%-38% of Type 2 DM patients had Hypomagnesemia, which has also contributed in developing microvascular complications such as Diabetic Retinopathy (DR) and Diabetic Nephropathy (DN). Various studies have suggested that Magnesium supplementation in Type 2 DM patients with Hypomagnesemia have shown beneficial effects on insulin sensitivity and glucose metabolism. Aim and objectives: To study the prevalence of Hypomagnesemia in Type 2 DM patients and to study the association of Hypomagnesemia with microvascular complications such as DR and DN. Materials and methods: It is a hospital based Observational study carried out in 2022 for a period of 1 year including 60 patients fulfilling the ADA criteria for diagnosing T2DM and patients with Diabetic Retinopathy and Diabetic Nephropathy, and excluding patients with Malabsorption, Chronic diarrhoea, Renal Failure on diuretic therapy, Sepsis, Pancreatitis. Serum Magnesium levels of 1.6 mg/dl � 2.6 mg/dl is considered as normal range. Serum Magnesium were measured using Xylidyl blue colorimetric method. Results: The Mean age of the patients in our study was 55.89 years. Among 60 patients diagnosed with Diabetes Mellitus, 42 patients had Hypomagnesemia, 18 patients had Normomagnesemia (p- value: <0.0001). Patients with an HbA1c levels > 7% had Hypomagnesemia when to compared to patients with HbA1c <7% with a significant p value of 0.009. Hypomagnesemia was also associated with Diabetic Retinopathy and Diabetic Nephropathy with a significant p-value of 0.013 and 0.009 respectively. Conclusion: In our study, it has shown that patients with uncontrolled T2DM had Hypomagnesemia, which is also associated with micro-vascular complications of T2DM such as DR and DN.

Research progress of radiation nephropathy / 中华放射医学与防护杂志

Radiotherapy is an important treatment for malignant tumors. However, it is also one cause of damage to local normal tissues, such as radiation nephropathy, which is frequently induced during the radiotherapy of abdominal and pelvic tumors. The exact pathogenesis of radiation nephropathy is still unclear and is believed to be related mainly to factors including oxidative stress, cell aging, and gene changes presently. Moreover, there is a lack of effective treatments for radiation nephropathy. With an increase in the survival of tumor patients, radiation nephropathy has received increasing attention. This article mainly reviewed the research progress of radiation nephropathy from the aspects of pathogenesis and treatments, aiming to provide a reference for the research and clinical diagnosis and treatment of radiation nephropathy.

Traditional Chinese Medicine in Prevention and Treatment of Renal Fibrosis in Diabetic Nephropathy by Targeting Notch Signaling Pathway： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN） is one of the common chronic kidney diseases （CKD） worldwide and a major cause of end-stage renal disease （ESRD）， seriously threatening and affecting the life and health of the global population. Currently， the pathogenesis of DN is considered to be closely related to factors such as glucose metabolism disorders， abnormal lipid metabolism， oxidative stress， activation of inflammatory factors， autophagy， and cell apoptosis in the continuous high-glucose environment of the body. Renal fibrosis is an important pathological feature and ultimate pathological outcome of DN. Timely intervention in renal fibrosis is of significant clinical and practical importance for the prevention and treatment of DN. Due to the limitations of western medicine in treating DN， traditional Chinese medicine （TCM） intervention in the process of renal fibrosis in DN has been widely used as a routine and potential treatment method due to its multi-component， multi-effect， and multi-target effects， effectively delaying the progression of the disease. It has been found that the Notch signaling pathway plays an important role in the development and maintenance of homeostasis in the body， and abnormal activation of the Notch signaling pathway is associated with DN. Activation of this signaling pathway plays a key role in the process of renal fibrosis. This article reviewed the regulatory mechanism of the Notch signaling pathway in renal fibrosis in DN， focusing on the relationship between targeting Notch signaling pathway by Chinese medicinal monomers and prescriptions and renal fibrosis in DN in order to provide a theoretical basis for the development of new drugs， basic research， and clinical application of TCM in the prevention and treatment of DN.

Oxidative stress status and its correlation with UACR and Uβ2-MG levels in patients with diabetic nephropathy / 公共卫生与预防医学

Objective To analyze oxidative stress status and its correlation with urinary albumin creatinine ratio (UACR) and urinary β2 microglobulin (Uβ2-MG) in patients with diabetic nephropathy (DN), and to provide a theoretical basis for clinical evaluation of oxidative stress status in DN patients. Methods A total of 382 DN patients admitted to our hospital from January 2020 to December 2021 were selected. According to the 24h urinary microalbumin excretion rate (24h UAER), the patients were divided into mild renal injury group (20µg/min 2-MG levels in DN patients (r=-0.462, 0.413, P2-MG levels in DN patients (r=-0.438, -0.459, P2-MG to predict the oxidative stress status of DN patients was 0.689, the sensitivity was 79.84%, and the specificity was 83.45%. Conclusion Oxidative stress in DN patients can accelerate the pathological progression of nephropathy. The oxidative stress status is closely related to the levels of UACR and Uβ2-MG, which can be used to judge the oxidative stress of the body and prevent the pathological progression of nephropathy in DN patients.

Mechanism of Modified Shenqiwan in Relieving Renal Interstitial Fibrosis in Diabetic Mice Based on GSK-3β/CREB Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effects of modified Shenqiwan on renal function and fibrosis in diabetic nephropathy mice and explore the underlying mechanism based on the glycogen synthase kinase-3β （GSK-3β）/cyclic adenosine monophosphate （cAMP） response element-binding protein （CREB） signaling pathway. MethodFifty male db/db mice and 10 db/m mice were used in this study. The fifty db/db mice were randomly divided into model group， irbesartan group， and low-， medium-， and high-dose modified Shenqiwan groups. The 10 db/m mice were assigned to the normal group. The mice in the low-， medium-， and high-dose modified Shenqiwan groups were administered with modified Shenqiwan in the dosage form of suspension of Chinese medicinal granules by gavage， those in the irbesartan group were given irbesartan suspension by gavage， and those in the normal and model groups were given distilled water of equal volume by gavage. The intervention lasted for 12 weeks. The blood glucose levels， urine albumin-to-creatinine ratio （UACR）， and the protein expression levels of GSK-3β， CREB， transforming growth factor-β1 （TGF-β1）， E-cadherin， Vimentin， fibronectin （FN）， plasminogen activator inhibitor-1 （PAI-1）， and Collagen type Ⅳ （Coll Ⅳ） in the mouse kidneys were recorded before and after treatment. The extent of renal pathological damage was also observed. ResultCompared with the normal group， the model group showed significant increases in blood glucose levels， UACR levels， and the protein expression levels of GSK-3β， TGF-β1， E-cadherin， Vimentin， FN， PAI-1， and Coll Ⅳ in the kidneys （P<0.05）， decreased protein expression level of CREB （P<0.05）， and severe renal pathological damage. Compared with the model group， the low-， medium-， and high-dose modified Shenqiwan groups and the irbesartan group showed varying degrees of decreases in blood glucose levels， UACR levels， and the protein expression levels of GSK-3β， TGF-β1， E-cadherin， Vimentin， FN， PAI-1， and Coll Ⅳ in the kidneys （P<0.05）， increased expression level of CREB protein （P<0.05）， and improved renal pathological damage. ConclusionModified Shenqiwan can effectively reduce blood glucose levels， improve renal function， and alleviate fibrosis， and the mechanism of action is related to the inhibition of the GSK-3β/CREB signaling pathway.