Risk factors for lower renal compensation after nephrectomy: an analysis of living kidney donors in an Amazonian cohort / Fatores de risco para menor compensação renal pós-nefrectomia: análise de doadores de rim vivo em uma coorte amazônica

Abstract Introduction: Living donor kidney transplantation is considered the ideal renal replacement therapy because it has a lower complication rate and allows an efficient response to the high demand for grafts in the healthcare system. Careful selection and adequate monitoring of donors is a key element in transplantation. Individuals at greater risk of developing kidney dysfunction after nephrectomy must be identified. Objective: To identify risk factors associated with a renal compensation rate (CR) below 70% 12 months after nephrectomy. Methods: This observational retrospective longitudinal study included living kidney donors followed up at the Lower Amazon Regional Hospital between 2016 and 2022. Data related to sociodemographic variables, comorbid conditions and kidney function parameters were collected. Results: The study enrolled 32 patients. Fourteen (43.75%) had a CR < 70% 12 months after kidney donation. Logistic regression found obesity (Odds Ratio [95%CI]: 10.6 [1.7-65.2]), albuminuria (Odds Ratio [95%CI]: 2.41 [1.2-4.84]) and proteinuria (Odds Ratio [95%CI]: 1.14 [1.03-1.25]) as risk factors. Glomerular filtration rate was a protective factor (Odds Ratio [95% CI]: 0.92 [0.85-0.99]). Conclusion: Obesity, albuminuria and proteinuria adversely affected short-term renal compensation rate. Further studies are needed to uncover the prognostic implications tied to these risk factors. Our findings also supported the need for careful individualized assessment of potential donors and closer monitoring of individuals at higher risk.

Resumo Introdução: O transplante de rim de doador vivo é considerado a terapia renal substitutiva ideal por oferecer menor taxa de complicações e possibilitar uma resposta eficiente à grande demanda por enxertos no sistema de saúde. A seleção criteriosa e o acompanhamento adequado dos doadores constituem um pilar fundamental dessa modalidade terapêutica, sendo essencial a identificação dos indivíduos em maior risco de disfunção renal pós-nefrectomia. Objetivo: Identificar fatores de risco para uma Taxa de Compensação (TC) da função renal inferior a 70% 12 meses após a nefrectomia. Métodos: Estudo observacional, retrospectivo e longitudinal conduzido com doadores de rim vivo acompanhados no Hospital Regional do Baixo Amazonas entre 2016 e 2022. Foram coletados dados correspondentes a variáveis sociodemográficas, comorbidades e parâmetros de função renal. Resultados: Foram incluídos 32 pacientes na amostra final. Destes, 14 (43,75%) obtiveram TC < 70% 12 meses após a doação. A regressão logística identificou a obesidade (Odds Ratio [IC95%]: 10.6 [1.7-65.2]), albuminúria (Odds Ratio [IC95%]: 2.41 [1.2-4.84]) e proteinúria (Odds Ratio [IC95%]: 1.14 [1.03-1.25]) como fatores de risco. A taxa de filtração glomerular atuou como fator de proteção (Odds Ratio [IC95%]: 0.92 [0.85-0.99]). Conclusão: Obesidade, albuminúria e proteinúria demonstraram impacto negativo na taxa de compensação renal em curto prazo, o que reitera a necessidade de estudos acerca das implicações prognósticas desses fatores. Além disso, reforça-se a necessidade de avaliação cuidadosa e individualizada dos possíveis doadores, com acompanhamento rigoroso, especialmente para indivíduos de maior risco.

Nefropatía por IgA con microangiopatía trombótica / IgA nephropathy with thrombotic microangiopathy

INTRODUCTION: IgA nephropathy is the most common glomerulopathy in the world, it has a wide clinical expression, from asymptomatic to rapidly progressive glomerulonephritis. The definitive diagnosis is renal biopsy, within which the IgA pattern can be identified, including thrombotic microangiopathy. CLINICAL CASE: 28-year-old female patient, with a history of preeclampsia in the last pregnancy, presents high blood pressure, hematuria and proteinuria. Study begins with initially negative results. Renal biopsy confirms IgA nephropathy with thrombotic microangiopathy. DISCUSSION: Vascular damage is underestimated in IgA nephropathy. Thrombotic microangiopathy can be associated with various clinical manifestations, however when it is associated with IgA Nephropathy it is usually associated with proteinuria, arterial hypertension and elevation of creatinine. In the presence of microangiopathy, secondary causes must be ruled out. In general, there is no pathognomonic serological marker. Eventually patients could benefit from the use of eculizumab. CONCLUSION: IgA nephropathy is the most common glomerulopathy worldwide; there is a wide range of clinical presentations, among which thrombotic microangiopathy can be found. This presentation is associated with a higher risk of progression to end-stage renal disease.

INTRODUCCIÓN: La nefropatía por IgA es la glomerulopatía más frecuente en el mundo, tiene una amplia expresión clínica, desde asintomática hasta glomerulonefritis rápidamente progresivas. El diagnóstico definitivo es la biopsia renal, dentro de las cuales se puede identificar el patrón de la IgA, dentro de los cuales está la microangiopatía trombótica. CASO CLÍNICO: Paciente femenina 28 años, con antecedentes de preeclampsia en último embarazo, presenta hipertensión arterial, hematuria y proteinuria. Se inicia estudio con resultados inicialmente negativos. Biopsia renal confirma nefropatía por IgA con microangiopatía trombótica. DISCUSIÓN: En la nefropatía por IgA se subestima el daño vascular. La microangiopatía trombótica se puede asociar con varias manifestaciones clínicas, sin embargo, cuando está asociada a NIgA suele estar asociado con proteinuria, hipertensión arterial y elevación y creatinina. Ante la presencia de microangiopatía, se deben descartar causas secundarias de la misma. En general no existe un marcador serológico patognomónico. Eventualmente los pacientes se podrían beneficiar del uso de eculizumab. CONCLUSIÓN: La nefropatía por IgA es la glomerulopatía más frecuente a nivel mundial, existe una gran gama de presentaciones clínicas, dentro de las cuales se puede encontrar microangiopatía trombótica. Esta última presentación se asocia con mayor riesgo de progresión a enfermedad renal en etapa terminal.

Pharmacological Blockade of the Adenosine A2B Receptor Is Protective of Proteinuria in Diabetic Rats, through Affecting Focal Adhesion Kinase Activation and the Adhesion Dynamics of Podocytes.

Induction of the adenosine receptor A2B (A2BAR) expression in diabetic glomeruli correlates with an increased abundance of its endogenous ligand adenosine and the progression of kidney dysfunction. Remarkably, A2BAR antagonism protects from proteinuria in experimental diabetic nephropathy. We found that A2BAR antagonism preserves the arrangement of podocytes on the glomerular filtration barrier, reduces diabetes-induced focal adhesion kinase (FAK) activation, and attenuates podocyte foot processes effacement. In spreading assays using human podocytes in vitro, adenosine enhanced the rate of cell body expansion on laminin-coated glass and promoted peripheral pY397-FAK subcellular distribution, while selective A2BAR antagonism impeded these effects and attenuated the migratory capability of podocytes. Increased phosphorylation of the Myosin2A light chain accompanied the effects of adenosine. Furthermore, when the A2BAR was stimulated, the cells expanded more broadly and more staining of pS19 myosin was detected which co-localized with actin cables, suggesting increased contractility potential in cells planted onto a matrix with a stiffness similar to of the glomerular basement membrane. We conclude that A2BAR is involved in adhesion dynamics and contractile actin bundle formation, leading to podocyte foot processes effacement. The antagonism of this receptor may be an alternative to the intervention of glomerular barrier deterioration and proteinuria in the diabetic kidney disease.

Eclampsia atípica tardía: compromiso inusual con proteinuria, pero sin hipertensión / Late atypical eclampsia: unusual involvement with proteinuria, but without hypertension

RESUMEN Paciente primigesta de 27 años, sin antecedentes médicos de importancia y con un apropiado control prenatal, quien recibió atención por parto vaginal a las 39 semanas de gestación con anestesia epidural. Una hora después del parto, presentó cefalea holocraneana a predominio derecho, tratada con antiinflamatorios y relajantes muscular por indicación del servicio de neurología. Horas después de su alta, al tercer día posparto, presentó convulsiones tónico-clónicas bilaterales. Por un examen de orina con proteinuria (+) en tira reactiva y elevaciones discretas de la presión arterial, se solicitó un conteo de proteínas en 24 horas, con valores en 1094,5 mg (valor normal: 0-140). La resonancia magnética con contraste solicitada durante su admisión fue normal, recibiendo tratamiento con fenitoína y sulfato de magnesio durante su hospitalización. Fue dada de alta al quinto día, con controles posteriores por consultorio externo, sin cefalea, proteinuria y/o hipertensión.

ABSTRACT A 27-year-old primigravida patient without a relevant medical history and appropriate prenatal control received attention for vaginal delivery at 39 weeks of gestation. One -hour later, she experienced holocranial headache with right predominance, treated with anti-inflammatories and muscle relaxants by the indication of a neurologist. Hours after her discharge, on the third day post-partum, she developed bilateral tonic-clonic seizures.. Following a urine test in the emergency room with proteinuria (+) in a dipstick, we tested 24-hour protein count in 1094 mg (normal values 0-140). Magnetic resonance with contrast at admission was normal. She received Phenytoin and Magnesium Sulfate during her hospitalization. The evolution was favorable, and he was discharged at five days with ambulatory controls in the medical office without headache, proteinuria, and/or hypertension.

Points of view in nephrology: personalized management of IgA nephropathy, beyond KDIGO.

IgA nephropathy is the most common primary glomerulonephritis worldwide, and an important cause of kidney failure, as 20-40% of patients progress to renal replacement therapy 20-30 years after diagnosis. Its clinical presentation ranges from isolated microscopic hematuria to nephrotic syndrome, and even to a rapidly progressive course. Ethnicity and epigenetics play a key role in its clinical aggressiveness. Selection of patients at risk needing immunosuppressive treatment is a challenge for the nephrologist. Some active and chronic kidney lesions detected on kidney biopsy have been demonstrated to have prognostic value according to the Oxford Classification of IgA nephropathy, later validated by numerous studies. However, KDIGO 2021 guidelines still consider persistent proteinuria > 1 g/24 h to be the most relevant risk factor for the progression of IgA nephropathy and the only one requiring immunosuppressive treatment. KDIGO guidelines have proposed a therapeutic algorithm, but many patients present peculiar characteristics that are not addressed by the current guidelines, pointing to the need for alternative approaches. In these cases, a tailored approach to each patient should be followed in which clinical, histological, laboratory, social and ethical aspects must be considered. In this manuscript we present three cases of IgA nephropathy from different countries, highlighting many of the aspects encountered in clinical practice that illustrate an individualized approach to the treatment of these patients.

Desempeño del analizador de orinas Laura XL-Erba Mannheim en comparación con el iRICELL-Beckman Coulter en una población general / Performance of the Laura XL urine analyzer-Erba Mannheim in comparison with IRISCell-Beckman Coulter in a general population / Desempenho do analisador de urina Laura XL-Erba Mannheim em comparação com iRICELL-Beckman Coulter em uma população geral

Resumen Los objetivos del trabajo fueron evaluar el desempeño del analizador de orinas Laura XL® Erba Mannhein, por comparación con el analizador iRICELL® Beckman Coulter y valorar la determinación de proteínas urinarias semicuantitativas como tamizaje en su estudio, con el establecimiento de un punto de corte para su cuantificación. Se emplearon 225 muestras de orina procesadas en simultáneo. Se evaluó pH, densidad, turbidez, color, hemoglobina, glucosa, cetonas, nitritos, proteínas, número de tiras reactivas positivas; células epiteliales, leucocitos, hematíes y criterio de normalidad del sedimento por microscopía. Se cuantificaron las proteínas urinarias positivas por tiras en un Modular COBAS® 8000 (Hitachi-Roche). Se empleó el coeficiente de concordancia Kappa de Cohen (k) y el índice de correlación de Spearman. Se obtuvo escasa concordancia en turbidez (k=0,334), buena concordancia en color (k=0,681), hemoglobina (k=0,620), glucosa (k=0,677), cetonas (k=0,768), nitritos (k=0,827), tiras reactivas positivas (k=0,620), células epiteliales (k=0,783), leucocitos (k=0,745) y hematíes (k=0,609); muy buena concordancia en proteínas (k=0,842) y criterio de normalidad del sedimento (k=1,000). Correlación estadísticamente significativa en pH (r=0,8064; p<0,0001), densidad (r=1,000; p<0,0001) y proteína urinaria (rs=0,9157; p<0,0001) comparada con COBAS® 8000. Se concluyó un desempeño satisfactorio de Laura XL®; se muestra un rendimiento acorde a las necesidades y normativas de este laboratorio y se avala su utilidad como test de tamizaje para la valoración de proteínas urinarias. Se estableció, además, la cuantificación de orinas que presentaron 1+ o más por tira en Laura XL®. Se consideró realizar mejoras en el software.

Abstract The objectives of this work were to evaluate the performance of the Laura XL® Erba Mannheim urine analyzer, in comparison with the iRICELL® Beckman Coulter analyzer, and to assess the determination of semiquantitative urinary protein as screening in its study, establishing a cut-off point for its quantification. A total of 225 urine samples were simultaneously processed. pH, density, turbidity, colour, hemoglobin, glucose, ketones, nitrites, proteins, and number of positive reactive strips were evaluated; and epithelial cells, leukocytes, red blood cells and criteria for normality of the sediment were evaluated by microscopy. Positive urinary proteins per strip were quantified on a Modular COBAS® 8000 (Hitachi-Roche). Cohen's Kappa concordance coefficient (k) and Spearman's correlation index were used. Little agreement was obtained in turbidity (k=0.334), good agreement in colour (k=0.681), hemoglobin (k=0.620), glucose (k=0.677), ketones (k=0.768), nitrites (k=0.827), positive test strips (k=0.620), epithelial cells (k=0.783), leukocytes (k=0.745) and red blood cells (k=0.609); very good agreement for proteins (k=0.842) and sediment normality criteria (k=1,000). Statistically significant correlation in pH (r=0.8064; p<0.0001), density (r=1.000; p<0.0001), urinary protein (rs=0.9157; p<0.0001) compared with COBAS® 8000. A satisfactory performance of Laura XL® was concluded, showing a performance consistent with the needs and regulations of this institution, and its usefulness is endorsed as a screening test for the assessment of urinary proteins, establishing the quantification of urines that present 1+ or more per strip in Laura XL®. Software improvements are considered.

Resumo Os objetivos do trabalho foram avaliar o desempenho do analisador de urina Laura XL® Erba Mannheim, em comparação com o analisador iRICELL® Beckman Coulter, e avaliar a determinação de proteínas urinárias semiquantitativa como triagem em seu estudo, estabelecendo um ponto de corte para sua quantificação. Foram utilizadas 225 amostras de urina processadas simultaneamente. Foram avaliados pH, densidade, turbidez, cor, hemoglobina, glicose, cetonas, nitritos, proteínas, número de testes reativos positivos; células epiteliais, leucócitos, hemácias e critérios de normalidade do sedimento à microscopia. As proteínas urinárias positivas por teste foram quantificadas em um Modular COBAS® 8000 (Hitachi-Roche). Foram utilizados o coeficiente de concordância Kappa de Cohen (k) e o índice de correlação de Spearman. Escassa concordância foi obtida em turbidez (k=0,334), boa concordância em cor (k=0,681), hemoglobina (k=0,620), glicose (k=0,677), cetonas (k=0,768), nitritos (k=0,827), testes reativos positivos (k=0,620), células epiteliais (k=0,783), leucócitos (k=0,745) e hemácias (k=0,609); concordância muito boa para proteínas (k=0,842) e critérios de normalidade do sedimento (k=1,000). Correlação estatisticamente significativa em pH (r=0,8064 p<0,0001), densidade (r=1,000 p<0,0001), proteína urinária (rs=0,9157 p<0,0001) em comparação com COBAS® 8000. A conclusão é um desempenho satisfatório de Laura XL®, mostrando um rendimento consistente com as necessidades e normas deste laboratorio e sua utilidade é endossada como teste de triagem para avaliação de proteínas urinárias, estabelecendo também a quantificação de urinas que apresentaram 1+ ou mais por teste em Laura XL®. Melhorias no software são consideradas.

suPAR and WT1 modify the adhesion of podocytes and are related to proteinuria in class IV lupus nephritis.

Introduction: Lupus nephritis (LN) affects up to 60 % of the patients with Systemic Lupus Erythematosus (SLE) and renal damage progression is associated with proteinuria, caused in part by the integrity of the glomerular basement membrane (GBM) and by podocyte injury. The soluble urokinase plasminogen activator receptor (suPAR) and Wilms Tumor 1 (WT1) have been related to podocyte effacement and consequently with proteinuria which raises questions about its pathogenic role in LN. Objective: Define whether suPAR levels and WT1 expression influence in podocyte anchorage destabilization in LN class IV. Materials and methods: This is a cross-sectional study of cases and controls. We studied patients with SLE without renal involvement (n = 12), SLE and LN class IV with proteinuria ≤0.5 g/24 h (n = 12), LN class IV with proteinuria ≥0.5 g/24 h (n = 12) and compared them with renal tissue control (CR) (n = 12) and control sera (CS) (n = 12). The CR was integrated by cadaveric samples without SLE or renal involvement and the CS was integrated by healthy participants. The expression and cellular localization of WT1, urokinase-type plasminogen activator receptor (uPAR), ac-α-tubulin, vimentin, and ß3-integrin was assessed by immunohistochemistry (IHC). The concentration of suPAR in serum was analyzed by enzyme-linked immunosorbent assay (ELISA). Results: In patients with LN, the activation of anchoring proteins was increased, such as podocyte ß3-integrin, as well as the acetylation of alpha-acetyl-tubulin and uPAR, in contrast to the decrease in vimentin; interestingly, the cellular localization of WT1 was cytoplasmic and the number of podocytes per glomerulus decreased. The concentrations of suPAR was increased in patients with LN. Conclusion: The destabilization of podocyte anchorage modulated by ß3-integrin activation, and tubulin acetylation, associated with decreased WT1 cytoplasmic expression, and increased suPAR levels could be involved in kidney damage in patients with LN class IV.

Albuminuria and cardiovascular risk.

Cardiovascular risk (CVR) estimation is a fundamental tool for guiding therapy. Albuminuria indicates target organ damage in an accessible, economic and non-invasive manner. Improves high-risk patient identification, especially in chronic kidney disease (CKD) and diabetes mellitus (DM). In addition, anti-albuminuric treatments may improve CVR. This would position albuminuria as a guide and therapeutic objective. Although the capacity of albuminuria as an epidemiological CVR marker in specific populations (hypertension, CKD, DM) is accepted, its profile as a risk marker in the general population and as a therapeutic target is controversial. There is ambiguous evidence regarding its predictive capacity, added to the fact that treatments such as SLGT2 blockers reduce CVR events regardless of albuminuria presence or magnitude. This review analyzes the available evidence on albuminuria as a CVR marker, a treatment goal and therapeutic guide.

Diagnostic Usefulness of Antibodies Against M-type Phospholipase A2 Receptor (aPLA2R) in Primary Membranous Nephropathy in the Mexican Population.

OBJECTIVE: This study aimed to determine the frequency and diagnostic performance of antibodies against M-type phospholipase A2 receptors (aPLA2R) in subjects with idiopathic membranous nephropathy (IMN). MATERIALS AND METHODS: A diagnostic test study was conducted in a cohort of 160 patients from the nephrology outpatient clinic over a period of eight years. Serum samples were taken and analyzed from patients with a histological diagnosis of IMN with proteinuria greater than and less than 1 g in 24 hours and other glomerular diseases other than IMN with aPLA2R measurement by enzyme-linked immunosorbent assay (ELISA) (Euroimmun, Luebeck, Germany). RESULTS: In 22 of 160 patients, an aPLA2R concentration >9 RU/mL was found, and all these cases had IMN. The prevalence of seropositivity in cases with active IMN was 78% (21/27). All these correlations were statistically significant with a p<0.001. The area under the receiver operating characteristic (ROC) curve (AB-ROC) of aPLA2R was 0.87 (95%, CI: 78-0.96). CONCLUSIONS: The aPLA2R has adequate diagnostic usefulness to diagnose IMN in the selected population, especially in subjects with proteinuria greater than 1 gr/day, with a sensitivity of 78% and a specificity of 99%.

Imerslund-Gräsbeck Syndrome: Clinical Case

Introduction: Imerslund-Gräsbeck syndrome (IGS) is a rare congenital disorder characterized by decreased vitamin B12, megaloblastic anemia, and proteinuria. Clinical case: A 58-year-old woman with four episodes of generalized tonic movements whose paraclinical findings showed cyanocobalamin deficiency. The presence of gait disturbances and constitutional syndrome was reported upon questioning, which required further investigation. The extension tests confirmed type 1 IGS, so it was decided to continue the cyanocobalamin management and nutrition evaluation, with which an adequate evolution was achieved. The patient was eventually discharged. Conclusion: This pathology is low prevalence and mainly affects the first decade of life. It prefers the female sex and is characterized by a decrease in vitamin B12, which can predispose to other disorders such as ataxia and growth retardation.

Introducción: el síndrome de Imerslund-Gräsbeck es un trastorno congénito infrecuente caracterizado por disminución de la vitamina B12, anemia megaloblástica y proteinuria. Caso clínico: mujer de 58 años de edad con cuatro episodios de movimientos tónicos generalizados cuyos paraclínicos mostraban deficiencia de cianocobalamina, por lo que en el interrogatorio se reportaba la presencia de alteraciones en la marcha y síndrome constitucional que requería ampliar los estudios. Los exámenes de extensión confirmaron el síndrome de Imerslund-Gräsbeck tipo 1, de modo que se decidió continuar el manejo con cianocobalamina y valoración con nutrición, con lo que se obtuvo una adecuada evolución y se decidió dar egreso a la paciente. Conclusión: esta patología tiene una baja prevalencia y afecta principalmente a la primera década de la vida, tiene predilección por el sexo femenino y se caracteriza por una disminución de la vitamina B12, que puede predisponer a otras alteraciones como ataxia y retraso en el crecimiento.

Proteinuria en la infancia: a propósito de un caso de enfermedad de Dent

Introducción: la proteinuria en la edad pediátrica es una entidad relativamente frecuente, la cual puede ser fisiológica o patológica. La segunda, por una alteración a nivel glomerular con pérdida de proteínas de gran tamaño o a nivel tubular, caracterizada por pérdida de proteínas de bajo peso molecular y alteraciones en la excreción de iones. Entre las enfermedades hereditarias que cursan con proteinuria tubular, se ha descrito la enfermedad de Dent, una patología ligada al cromosoma X. Esta enfermedad se manifiesta principalmente en varones, pero las mujeres pueden ser portadoras y tener manifestaciones clínicas leves de la enfermedad. La primera descripción de esta enfermedad fue hecha por Dent y Friedman en 1964. La mayoría de los casos recientemente reportados han sido en China y Alemania. Objetivo: realizar una revisión general de la enfermedad de Dent y del enfoque diagnóstico de la proteinuria en la infancia con base en nuestro caso, para así, sospechar de esta enfermedad. Descripción del caso: se presenta el caso de un paciente masculino sin antecedentes prenatales ni personales de importancia, quien presenta proteinuria persistente desde los primeros meses de vida y a quien, a los 7 años de edad, se le documenta la presencia de una variante ya conocida en el gen CLCN5, causante de la enfermedad de Dent tipo 1. Discusión: la proteinuria persistente patológica en la infancia debe ser estudiada debido a su posible relación con patologías que pueden afectar la función renal. Además de la diferenciación de la proteinuria persistente, de origen glomerular y tubular, la evaluación de alteraciones en la excreción de electrolitos, puede guiarnos hacia la realización de estudios genéticos y, por ende, al diagnóstico de patologías infrecuentes como la enfermedad de Dent. Conclusión: el enfoque diagnóstico de causas poco frecuentes de proteinuria tubular en la infancia, como la enfermedad de Dent, requiere de la valoración conjunta entre nefrología pediátrica y genética clínica.

Background: In pediatric patients, proteinuria is a relatively frequent entity that can be physiological or pathological. The second one, due to an alteration at the glomerular level with the loss of large proteins or at the tubular level, characterized mainly by the loss of low molecular weight proteins and changes in the excretion of ions. Among the hereditary diseases that present with tubular proteinuria, Dent disease is a disease linked to the X chromosome. Therefore, it manifests essentially in males, but women can be carriers and have minor clinical manifestations of the disease. Dent and Friedman made the first description of this disease in 1964. Recently, most of the cases have been reported in China and Germany. Objective: To perform a revision of Dent disease, as well as the diagnostic approach of childhood proteinuria based in our case in order to suspect this disease. Case description: This is the case of a masculine patient, without relevant prenatal and personal antecedents, the son of a father with polycystic renal disease, who presents persistent proteinuria from the first months of life, and who, at seven years old, the presence of a variant in the CLCN5 gene -causing of type 1 Dent disease- was documented. Discussion: The persistent pathological proteinuria in childhood must be studied due to its possible relation with pathologies that could affect renal function. Moreover, the differentiation among glomerular and tubular proteinuria can guide us to perform additional studies, including genetic tests to diagnose infrequent pathologies like Dent disease. Conclusion: The diagnostic approach to rare causes of tubular proteinuria in childhood, such as Dent's disease, requires joint assessment between pediatric nephrology and clinical genetics.

Renal Manifestations of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Systematic Review of 71 Cases.

Unlike other adverse drug reactions, visceral organ involvement is a prominent feature of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and correlates with mortality. The aim of this study was to systematically review cases published in PubMed-indexed, peer-reviewed journals in which patients had renal injury during the episode of DRESS syndrome (DS). We found 71 cases, of which 67 were adults and 56% were males. Female sex was associated with higher mortality. Chronic kidney disease (CKD) was present in 14% of patients who developed acute kidney injury (AKI) during DS. In 21% of cases, the kidneys were the only visceral organ involved, while 54% of patients had both liver and kidney involvement. Eosinophilia was absent in 24% of patients. The most common classes of medication associated with renal injury in DS were antibiotics in 34%, xanthine oxidase inhibitors in 15%, and anticonvulsants in 11%. Among antibiotics, vancomycin was the most common culprit in 68% of patients. AKI was the most common renal manifestation reported in 96% of cases, while isolated proteinuria or hematuria was present in only 4% of cases. In cases with AKI, 88% had isolated increase in creatinine and decrease in glomerular filtration (GFR), 27% had AKI concomitantly with proteinuria, 18% had oliguria, and 13% had concomitant AKI with hematuria. Anuria was the rarest manifestation, occurring in only 4% of patients with DS. Temporary renal replacement therapy was needed in 30% of cases, and all but one patient fully recovered renal function. Mortality of DS in this cohort was 13%, which is higher than previously reported. Medication class, latency period, or pre-existing CKD were not found to be associated with higher mortality. More research, particularly prospective studies, is needed to better recognize the risks associated with renal injury in patients with DS. The development of disease-specific biomarkers would also be useful so DS with renal involvement can be easier distinguished from other eosinophilic diseases that might affect the kidney.

Rapamycin treatment induces tubular proteinuria: role of megalin-mediated protein reabsorption.

Introduction: Rapamycin is an immunosuppressor that acts by inhibiting the serine/threonine kinase mechanistic target of rapamycin complex 1. Therapeutic use of rapamycin is limited by its adverse effects. Proteinuria is an important marker of kidney damage and a risk factor for kidney diseases progression and has been reported in patients and animal models treated with rapamycin. However, the mechanism underlying proteinuria induced by rapamycin is still an open matter. In this work, we investigated the effects of rapamycin on parameters of renal function and structure and on protein handling by proximal tubule epithelial cells (PTECs). Methods: Healthy BALB/c mice were treated with 1.5 mg/kg rapamycin by oral gavage for 1, 3, or 7 days. At the end of each treatment, the animals were kept in metabolic cages and renal function and structural parameters were analyzed. LLC-PK1 cell line was used as a model of PTECs to test specific effect of rapamycin. Results: Rapamycin treatment did not change parameters of glomerular structure and function. Conversely, there was a transient increase in 24-h proteinuria, urinary protein to creatinine ratio (UPCr), and albuminuria in the groups treated with rapamycin. In accordance with these findings, rapamycin treatment decreased albumin-fluorescein isothiocyanate uptake in the renal cortex. This effect was associated with reduced brush border expression and impaired subcellular distribution of megalin in PTECs. The effect of rapamycin seems to be specific for albumin endocytosis machinery because it did not modify renal sodium handling or (Na++K+)ATPase activity in BALB/c mice and in the LLC-PK1 cell line. A positive Pearson correlation was found between megalin expression and albumin uptake while an inverse correlation was shown between albumin uptake and UPCr or 24-h proteinuria. Despite its effect on albumin handling in PTECs, rapamycin treatment did not induce tubular injury measured by interstitial space and collagen deposition. Conclusion: These findings suggest that proteinuria induced by rapamycin could have a tubular rather than a glomerular origin. This effect involves a specific change in protein endocytosis machinery. Our results open new perspectives on understanding the undesired effect of proteinuria generated by rapamycin.

Effect of clinical treatments for metabolic syndrome on albuminuria: a systematic review protocol

Introduction:Metabolic syndrome (MetS) predicts cardiovascular disease, and patients with this condition and type 2 diabetes have increased albuminuria, significantly impacting cardiovascular mortality and kidney disease progression. A considerable number of interventions to control MetS exist and are considered efficient, including the use of medication and changes in lifestyle. However, which approaches are effective in controlling albuminuria remains unclear. This systematic review protocol aims to map in the available literature whether lifestyle, medication, and surgical intervention for MetS have an impact on reducing albuminuria in adult patients. Methods: The Joanna Briggs Institute methodology for systematic reviews will be followed. Cochrane Database of Systematic Reviews, Scopus, Embase, and MEDLINE/PubMed databases will be used. For the Gray Literature, the DART-Europe E-theses Portal. There will be no language restriction. Studies written after 2009 will be included due to the consensus and definition of metabolic syndrome. This review will include studies considering pharmacological and non-pharmacological treatments for controlling albuminuria in patients with MetS. Studies where MetS is described in children and adolescents, animals, pregnant women, and patients with type 1 diabetes will be excluded. First, the selection will be based on reading the title and summary of the texts retrieved in the search strategy, followed by reading the relevant texts in full by two reviewers. After the selection of the studies, the extraction of the data, analysis, and synthesis will be conducted according to the JBI methodology

Comparison of Urinary Protein/Creatinine Ratio as an Alternative to 24-h Proteinuria in Lupus Nephritis: TUNARI Study.

BACKGROUND: Lupus nephritis (LN) occurs in approximately 50% of people with systemic lupus erythematosus (SLE). The 24-h proteinuria (gold standard) is measured among other tests for the control and monitoring of LN activity. This study investigates the use of the protein/creatinine ratio (PCR) as an alternative for the detection of proteinuria and its accuracy compared to the gold standard in a predominantly non-white population. METHODS: This was a prospective study conducted in Salvador, Brazil, between December 2021 and May 2022. We invited adult patients diagnosed with SLE and LN, regardless of their disease activity. The estimation of the PCR and 24-h proteinuria was performed using conventional methods. The analysis used was Spearman's r correlation coefficient (rs), coefficient of determination (r2), and concordance by the Bland-Altman method. A specific sensitivity was measured by the ROC curve with its respective cut-off by the Youden Index. RESULTS: We compared 112 samples of 75 patients with LN, with a mean age of 34.5 ± 11.8 years. Of these patients, 85% were women, 87.9% were non-white. A high degree of correlation was observed between PCR with 24-h proteinuria (rs = 0.77 and r2 = 0.59). The ROC analysis shows an area under the curve of 0.92 and the cut-off point calculated by the Youden Index was 0.78 with a sensitivity of 90.0% and specificity of 82%. However, the Bland-Altman graph indicated decreasing concordance as the degree of proteinuria increased, despite showing concordance at high levels of proteinuria. CONCLUSION: The PCR shows high sensitivity to follow-up patients with LN when compared with 24-h proteinuria. Our findings suggest that PCR is a useful parameter for the evaluating and monitoring patients in complete remission. However, in cases of partial remission, the utility of PCR is limited.

Albumin-to-protein ratio in spot urine samples for analysis of proteinuria selectivity in chronic kidney disease / Razão albumina/proteína em amostras isoladas de urina para análise da seletividade de proteinúria na doença renal crônica

ABSTRACT Introduction: The albumin-to-creatinine ratio and total protein-to-creatinine ratio in spot urine samples have already been validated as surrogates for 24-hour albuminuria and proteinuria measurements. Thus, we hypothesized that the type of proteinuria, detected by the electrophoretic pattern of 24-hour urine, could be predicted by the simple proportion of albumin in the total urine protein content, using the albumin-to-protein ratio (APR). Our study sought to validate the use of APR as a cheaper substitute for urinary protein electrophoresis (UPE). Methods: Using different mathematical models, we compared, the albumin fraction in 24-hour urine samples by electrophoresis and the APR ratio in spot samples from 42 outpatients with chronic kidney disease (CKD). Results: A strong log-order correlation r = 0.84 (0.75-0.92; 95% CI, p = 0.001) was observed between APR and the albumin fraction in the UPE. Conclusion: The APR can substitute electrophoresis in CKD outpatients.

Resumo Introdução: A utilização da razão albumina/creatinina e da razão proteína total/creatinina em amostras isoladas de urina já foram validadas como substitutos para a albuminúria e proteinúria em 24 horas. Assim, nossa hipótese é que o tipo de proteinúria, dado pelo padrão eletroforético da urina de 24 horas, poderia ser previsto pela simples proporção de albumina no conteúdo total de proteínas na urina, utilizando a razão albumina/proteína (RAP). O presente estudo procurou validar o uso da RAP como um substituto mais prático e de menor custo da eletroforese de proteínas urinárias (EPU). Métodos: Foram utilizados diferentes modelos matemáticos a fim de comparar a fração de albumina pela eletroforese em amostras de urina de 24 horas e a RAP em amostras isoladas em 42 pacientes ambulatoriais com doença renal crônica. Resultados: Foi observada uma forte correlação logarítmica r = 0,84 (0,75-0,92; 95% CI, p = 0,001) entre a RAP e a fração de albumina pela EPU. Conclusão: A RAP pode substituir a eletroforese urinária em pacientes renais crônicos ambulatoriais.

Chronic kidney disease prevention campaign: relationship between proteinuria and elderly people / Campanha de prevenção de doença renal crônica: relação entre proteinúria e idosos

ABSTRACT Objective: To verify the relationship between the presence of proteinuria as a renal injury marker in elderly without history of systemic arterial hypertension and cardiovascular diseases. A cross-sectional study was developed from January 2014 to December 2019, through kidney disease prevention campaigns promoted by the Federal University of Ceará in the city of Fortaleza. Methods: The sample consisted of 417 elderlies. A questionnaire was used to characterize individuals and assess previous diseases, and urinalysis reagent strips were used to assess proteinuria. Results: Statistically significant differences (p < 0.05) and moderate effect sizes were found for blood pressure levels (CI 0.53-0.93), systolic blood pressure, and diastolic blood pressure (CI 0.21-0.61). Significant differences in capillary glycemia were also found between groups (p = 0.033), but with a low effect size (0.02-0.42). The group with comorbidities was 2.94 times more likely to have proteinuria than those without comorbidities (OR 2.94, CI 1.55-4.01; p < 0.05). In the group without cardiovascular disease/high blood pressure, a statistically significant association was found for previous diabetes and proteinuria (p = 0.037), presenting 2.68 times higher risk of proteinuria in those with diabetes mellitus (OR 2.68, CI 1.05-6.85). Significant association was also found between age groups, with the older group having 2.69 times higher risk of developing proteinuria (75 to 90 compared to 60 to 74 years) (CI 1.01-7.16; p = 0.045). Conclusion: Even without systemic arterial hypertension or cardiovascular disease, diabetes and older age can be considered high risk factors for proteinuria.

Resumo Objetivo: Verificar a relação entre a presença de proteinúria como marcador de lesão renal em idosos sem histórico de hipertensão arterial sistêmica e doenças cardiovasculares. Um estudo transversal foi desenvolvido de Janeiro de 2014 a Dezembro de 2019, por meio de campanhas de prevenção a doenças renais promovidas pela Universidade Federal do Ceará, na cidade de Fortaleza. Métodos: A amostra foi composta por 417 idosos. Um questionário foi usado para caracterizar indivíduos e avaliar doenças prévias, e foram utilizadas tiras reagentes de urinálise para avaliar proteinúria. Resultados: Diferenças estatisticamente significativas (p < 0,05) e tamanhos de efeito moderados foram encontrados para níveis de pressão arterial (IC 0,53-0,93), pressão arterial sistólica e pressão arterial diastólica (IC 0,21-0,61). Também foram encontradas diferenças significativas na glicemia capilar entre grupos (p = 0,033), mas com um tamanho de efeito baixo (0,02-0,42). O grupo com comorbidades apresentou 2,94 vezes mais probabilidade de ter proteinúria do que aqueles sem comorbidades (OR 2,94; IC 1,55-4,01; p < 0,05). No grupo sem doença cardiovascular/hipertensão, foi encontrada uma associação estatisticamente significativa para diabetes anterior e proteinúria (p = 0,037), apresentando risco 2,68 vezes maior de proteinúria naqueles com diabetes mellitus (OR 2,68; IC 1,05-6,85). Também foi encontrada uma associação significativa entre faixas etárias, com o grupo mais velho apresentando risco 2,69 vezes maior de desenvolver proteinúria (75 a 90 em comparação com 60 a 74 anos) (IC 1,01-7,16; p = 0,045). Conclusão: Mesmo sem hipertensão arterial sistêmica ou doença cardiovascular, o diabetes e a idade avançada podem ser considerados fatores de alto risco para proteinúria.

German Shorthaired Pointer dogs with exfoliative cutaneous lupus erythematosus develop immune-complex membranous glomerulonephropathy.

German Shorthaired Pointer (GSHP) dogs with a UNC93B1 gene mutation develop exfoliative cutaneous lupus erythematosus (ECLE) and kidney disease resembling lupus nephritis in humans. The objective of this study was to characterize the kidney disease by light microscopy, immunofluorescence, and electron microscopy in a population of GSHP dogs with ECLE. Medical records were reviewed, and light microscopy of kidneys from 7 GSHP dogs with a previous histologic diagnosis of ECLE was performed. Immunofluorescence of fresh-frozen kidney from 1 dog and transmission electron microscopy of kidney from that dog and 2 additional dogs were performed. Five of 7 dogs had proteinuria diagnosed by urinalysis or urine protein-to-creatinine ratio. Two of 7 dogs were intermittently hypoalbuminemic, and none were azotemic. Histologic findings included early (2 dogs) to late (5 dogs) membranous glomerulonephropathy characterized by mild-to-severe glomerular capillary loop thickening and tubular proteinosis. In all 7 cases, trichrome staining revealed red granular immune deposits on the subepithelial surface of the glomerular basement membrane. Immunofluorescence revealed strong granular labeling for immunoglobulins and complement protein C3. Electron microscopy demonstrated subepithelial electron-dense immune deposits encircled by the remodeled glomerular basement membrane. These findings are diagnostic of immune-complex membranous glomerulonephropathy and are similar to class V lupus in humans. This cohort of GSHP dogs with ECLE developed immune-complex membranous glomerulonephropathy, which we hypothesize is a manifestation of systemic lupus erythematosus. GSHP dogs with ECLE should undergo clinical evaluation of renal function for early identification and treatment.

Older patients are less prone to fast decline of renal function: a propensity-matched study.

PURPOSE: Despite CKD is common among older patients, and although factors associated with CKD progression have been explored over decades, little is known about the decline of renal function specifically in older individuals. METHODS: We included adult patients with CKD on conservative management in a propensity-score matched study 1:1 older (> 65 year) and young (≤ 65 yr). Factors associated with the slope of the decline of eGFR such as proteinuria, initial eGFR, diabetes, sex, and use of angiotensin-converting enzyme inhibitor/angiotensin receptor block (ACEI/ARB) were analyzed. Inclusion criteria were at least two consultations in the service and an initial eGFR lower than 45 ml/min/m2, in the period between January 2012 and December 2017. RESULTS: Crude analysis of eGFR decline shows a slower progression of older patients when compared to younger patients in both absolute change [- 2.0 (- 4.5, - 1.0) vs. -3.0 (- 7.0, - 1.0) ml/min/1.73m2, p < 0.001] and slope of eGFR reduction [- 2.2 (- 4.4, - 1.0) vs. 3.1 (- 6.7, - 1.2)) ml/min/1.73m2, p < 0.001]. Patients considered fast progressors (> 5 ml/min/1.73 m2/year decline in eGFR) were less likely to be older (35.2% young vs. 22.0% older, p < 0.001). Adjusted logistic multivariate regression confirmed that older patients had less odds ratio of eGFR decline, independently of the presence of proteinuria, diabetes, ACEI/ARB use, sex, baseline eGFR, baseline phosphate and baseline 25(OH) vitamin D. CONCLUSION: Older patients present slower CKD progression even after multiple adjustments. This information should be taken into consideration while treating these patients on conservative management and should be kept in mind while planning dialysis start.

Proteinuria and Electrophoretic Pattern in Dogs with Comorbidities Associated with Chronic Kidney Disease.

In animals with chronic pathologies, the detection of proteinuria via the proteinuria: creatininuria ratio (UPC) and urinary protein electrophoresis allows for the early diagnosis of chronic kidney disease (CKD). The objective of this work was to identify and determine the magnitude of proteinuria and its electrophoretic pattern characterization in dogs with chronic diseases pathophysiologically related to proteinuria. With the studied patients, five groups were formed. The control group (CG) contained non-proteinuric cases. The cases with proteinuria were classified into four groups according to the concurrent disease: chronic inflammatory diseases (IG), neoplasms (NG), heart diseases (HG), and endocrine diseases (EG). For the statistical analysis, descriptive statistics and non-parametric tests were used. Data from 264 dogs were obtained; in the disease groups, proteinuria was observed in more than 30% as the only finding of kidney disease, evidencing a greater risk factor for proteinuria in the HG group (OR 4.047, CI 1.894-8.644, p < 0.0001). In the HG, NG, and EG groups, a higher frequency of glomerular pattern (GEP) related to glomerular hypertension was observed; in the IG, a higher frequency of mixed pattern (MEP) was observed. These findings are secondary to the hyperfiltration process that affects the glomerulus and the renal tubule.