Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group.

The histopathological lesions, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are entities without immune complex deposits which can cause podocyte injury, thus are frequently grouped under the umbrella of podocytopathies. Whether MCD and FSGS may represent a spectrum of the same disease remains a matter of conjecture. Both frequently require repeated high-dose glucocorticoid therapy with alternative immunosuppressive treatments reserved for relapsing or resistant cases and response rates are variable. There is an unmet need to identify patients who should receive immunosuppressive therapies as opposed to those who would benefit from supportive strategies. Therapeutic trials focusing on MCD are scarce, and the evidence used for the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline for the management of glomerular diseases largely stems from observational and pediatric trials. In FSGS, the differentiation between primary forms and those with underlying genetic variants or secondary forms further complicates trial design. This article provides a perspective of the Immunonephrology Working Group (IWG) of the European Renal Association (ERA) and discusses the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases focusing on the management of MCD and primary forms of FSGS in the context of recently published evidence, with a special emphasis on the role of rituximab, cyclophosphamide, supportive treatment options and ongoing clinical trials in the field.

Cystic phenotype and chronic kidney disease in autosomal dominant Alport syndrome.

BACKGROUND: Autosomal dominant Alport Syndrome (ADAS), also known as thin basement membrane disease (TBMD), is caused by pathogenic variants in the COL4A3 and COL4A4 genes. A cystic phenotype has been described in some patients with TBMD, but no genetic studies have been performed. We conducted a genetic and radiologic investigation in a cohort of ADAS patients to analyze the prevalence of multicystic kidney disease (MKD) and its association with chronic kidney disease (CKD). METHODS: This was a retrospective single-center cohort study. Thirty-one patients showing pathogenic or likely pathogenic variants in COL4A3 or COL4A4 from a cohort of 79 patients with persistent microscopic hematuria were included. Mean follow-up was 9.4 ± 9.6 years. The primary objective of the study was to determine the prevalence of MKD in the cohort of ADAS patients. Secondary objectives were to determine risk factors associated with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 at the time of genetic and radiologic evaluation and to investigate the coexistence of other genetic abnormalities associated with familial hematuria and cystic kidney disease. RESULTS: MKD was found in 16 patients (52%). Mean number of cysts per kidney was 12.7 ± 5.5. No genetic abnormalities were found in a panel of 101 other genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney disease. A greater number of patients with MKD had an eGFR <45 mL/min/1.73 m2 (63% vs 7%, P = .006) and more advanced CKD than patients without MKD. The annual rate of eGFR decline was greater in patients with MKD: -1.8 vs 0.06 mL/min/1.73 m2/year (P = .009). By multivariable linear regression analysis, the main determinants of eGFR change per year were time-averaged proteinuria (P = .002) and MKD (P = .02). CONCLUSION: MKD is commonly found in ADAS and is associated with a worse kidney outcome. No pathogenic variants were found in genes other than COL4A3/COL4A4.

Documento de consenso del Grupo de Estudio de Enfermedades Glomerulares de la Sociedad Española de Nefrología (GLOSEN) para el diagnóstico y tratamiento de la nefritis lúpica / Consensus document of the Spanish Group for the Study of the Glomerular Diseases (GLOSEN) for the diagnosis and treatment of lupus nephritis

Un número importante de pacientes con lupus eritematoso sistémico (entre 20 a 60%, según diferentes series) desarrolla nefritis lúpica en el curso de su evolución, lo que influye directamente en su calidad de vida y pronóstico vital. En años recientes, el mayor conocimiento sobre la patogénesis del lupus sistémico y de la nefritis lúpica ha permitido avances relevantes en el abordaje diagnóstico y en el tratamiento de estos pacientes, lográndose desarrollar fármacos dirigidos específicamente a bloquear vías patogénicas claves de la enfermedad. Alentadoramente estos agentes inmunomoduladores han demostrado en ensayos clínicos aleatorizados, y bien ponderados, buena eficacia clínica a mediano plazo, definida como remisión de proteinuria y preservación de la función renal, con un aceptable perfil de seguridad y buena tolerabilidad del paciente. Todo esto ha permitido reducir el uso de corticoides y de otras terapias potencialmente más tóxicas, así como incrementar el uso de terapias combinadas. El presento documento de consenso realizado por el Grupo de Trabajo de Enfermedades Glomerulares de la Sociedad Española de Nefrología (GLOSEN) recoge de manera práctica y resumida, pero rigurosa, la mejor evidencia actual disponible acerca del diagnóstico, tratamiento y seguimiento del paciente con nefritis lúpica, incluyendo casos de situaciones especiales, con el objetivo principal de brindar información actualizada y recomendaciones clínicas bien fundamentadas a los médicos tratantes, para mejorar el enfoque diagnóstico y terapéutico a nuestro pacientes. (AU)

A significant number of patients with systemic lupus erythematosus (between 20% to 60% according to different reported series) develop lupus nephritis in the course of its evolution, which directly influences their quality of life and vital prognosis. In recent years, the greater knowledge about the pathogenesis of systemic lupus and lupus nephritis has allowed relevant advances in the diagnostic approach and treatment of these patients, achieving the development of drugs specifically aimed at blocking key pathogenic pathways of the disease. Encouragingly, these immunomodulatory agents have shown in well-powered, randomized clinical trials good clinical efficacy in the medium-term, defined as proteinuria remission and preservation of kidney function, with an acceptable safety profile and good patient tolerability. All this has made it possible to reduce the use of corticosteroids and other potentially more toxic therapies, as well as to increase the use of combined therapies. The present consensus document carried out by the Glomerular Diseases Working Group of the Spanish Society of Nephrology (GLOSEN), collects in a practical and summarized, but rigorous way, the best currently available evidence about the diagnosis, treatment, and follow-up of lupus nephritis patients, including cases of special situations, with the main objective of providing updated information and well-founded clinical recommendations to treating physicians, to improve the diagnostic and therapeutic approach to our patients. (AU)

Nuevos retos en las nefritis tubulointersticiales inducidas por fármacos / New challenges in tubulointerstitial nephritis induced by drugs

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Kidney injury after sodium phosphate solution beyond the acute renal failure / Daño renal después de preparación colónica con soluciones de fosfato. Más allá del fracaso renal agudo

Antecedentes y objetivos: La colonoscopia con polipectomía con fines de cribado reduce la incidencia del cáncer colorrectal y la mortalidad por esta enfermedad. Una preparación colónica aceptable es una de las claves para conseguir mejores resultados con esta técnica. Las soluciones de fosfato de sodio oral (OSP) fueron muy utilizadas en la década de los noventa del siglo pasado. Su eficacia era similar a la de las soluciones de polietilenglicol (PEG), pero más baratas y con una administración sencilla. Se han descrito series de casos de pacientes con insuficiencia renal aguda provocada por OSP. Sin embargo, en cohortes amplias de pacientes no se observó ninguna diferencia en la incidencia de daño renal entre estas dos soluciones. Métodos: Entre 2006 y 2009 identificamos 12 casos de nefropatía por fosfato tras preparación con OSP para colonoscopia. Se realizó el seguimiento de todos los pacientes durante 6 meses. Todos los pacientes habían recibido una única dosis. Resultados: Analizamos 12 casos de nefropatía por fosfato; 3 se manifestaron con IRA y 9 presentaron daño renal crónico. Cuatro de los casos se confirmaron mediante biopsia renal. Un paciente con IRA precisó hemodiálisis en el momento del diagnóstico, sin que experimentara recuperación posterior. Dos pacientes (ambos con daño crónico) recuperaron totalmente su función renal anterior. Los demás pacientes (9) presentaron una pérdida media en la filtración glomerular estimada de 24ml/min/1,73m2. Conclusiones: El uso de OSP puede ocasionar daño renal tanto agudo como crónico. Sin embargo, el daño crónico fue el más frecuente. Ambas formas de presentación suponen una pérdida considerable e irreversible de función renal. Nuevos estudios que analicen el daño renal secundario a preparación colónica deben considerar estos dos patrones distintos de daño (AU)

Background and objectives: Screening colonoscopy with polipectomy reduces colonorectal cancer incidence and mortality. An adequate bowel cleansing is one of the keys to achieving best results with this technique. Oral sodium phosphate solution (OSP) had a widespread use in the 90s decade. Its efficacy was similar to polyethylene glycol (PEG) solution, but with less cost and convenient administration. Series of patients with acute renal failure due to OSP use have been reported. However, large cohorts of patients found no difference in the incidence of renal damage between these two solutions. Methods: From 2006 to 2009 we identified twelve cases of phosphate nephropathy after colonoscopy prepared with OSP. All patients were followed up to six months. All patients had received just a single dose. Results: We analyzed 12 cases with phosphate nephropathy; three patients debuted with AKI and nine patients had chronic renal injury. Four cases were confirmed with renal biopsy. One patient with AKI needed hemodialysis at diagnosis without subsequent recovery. Two patients (both with chronic damage) fully recovered their previous renal function. The remaining patients (nine) had an average loss of estimated glomerular filtration rate of 24ml/min/1.73m2. Conclusions: The use of OSP can lead to both acute and chronic renal damage. However, chronic injury was the most common pattern. Both forms of presentation imply a significant and irreversible loss of renal function. Further studies analyzing renal damage secondary to bowel cleaning should consider these two different patterns of injury (AU)

Embarazo en mujeres en diálisis crónica: revisión / Pregnancy in women on chronic dialysis: a review

La frecuencia de embarazos en mujeres en diálisis es extremadamente baja, aunque el porcentaje de gestaciones con éxito ha aumentado a lo largo de los años, siendo, según distintas series, superior al 70%. Estos embarazos no están exentos de complicaciones tanto para la madre como para el feto, el manejo de las cuales requiere el trabajo conjunto del nefrólogo, el ginecólogo, el enfermero y el nutricionista. A día de hoy no es posible encontrar un tratamiento sistemático nefrológico y ginecológico en este tipo de pacientes. Las principales medidas que se deberían adoptar incluirían: aumento del tiempo de diálisis, mantener bajos niveles de urea prediálisis, evitar hipotensiones e hipertensión materna, así como infecciones urinarias y fluctuaciones electrolíticas. Se requiere, además, una adecuada monitorización fetal (AU)

The frequency of pregnancy in women on dialysis is extremely low, but the percentage of successful pregnancies in this context has increased over the years, with some studies placing the survival rate above 70%. These pregnancies are not exempt from both maternal and foetal complications, and so their management requires the joint efforts of nephrologists, gynaecologists, nurses, and nutritionists. Currently, we have been unable to establish consistent systematic treatment from both nephrological and gynaecological specialists in these patients. The main changes that need to be made are: increased time on dialysis, maintaining low levels of pre-dialysis urea, avoiding: maternal hypertension and hypotension, anaemia, urinary tract infections, and fluctuations in electrolytes. Adequate foetal monitoring is also necessary (AU)