Autosomal dominant ApoA4 mutations present as tubulointerstitial kidney disease with medullary amyloidosis.

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a chr11:116693454 C>T (hg19) variant encoding the missense mutation p.D33N. Both mutations are unique to affected families, evolutionarily conserved and predicted to expand the amyloidogenic hotspot in the ApoA4 structure. Clinically affected individuals suffered from CKD with a bland urinary sediment and a mean age for kidney failure of 64.5 years. Genotyping identified 48 genetically affected individuals; 44 individuals had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73 m2, including all 25 individuals with kidney failure. Significantly, 11 of 14 genetically unaffected individuals had an eGFR over 60 ml/min/1.73 m2. Fifteen genetically affected individuals presented with higher plasma ApoA4 concentrations. Kidney pathologic specimens from four individuals revealed amyloid deposits limited to the medulla, with the mutated ApoA4 identified by mass-spectrometry as the predominant amyloid constituent in all three available biopsies. Thus, ApoA4 mutations can cause autosomal dominant medullary amyloidosis, with marked amyloid deposition limited to the kidney medulla and presenting with autosomal dominant CKD with a bland urinary sediment. Diagnosis relies on a careful family history, APOA4 sequencing and pathologic studies.

Autosomal dominant chronic tubulointerstitial nephropathy: do not forget amyloidosis.

Amyloidosis is a rare cause of inherited kidney disease, with most variants responsible for prominent glomerular involvement. In this issue, Kmochová et al. reported the first description of autosomal dominant medullary amyloidosis due to apolipoprotein A4 variants, resulting in slowly progressive chronic kidney disease with minimal proteinuria. Combining next-generation sequencing with histopathological studies incorporating Congo red staining and mass spectrometry should be considered in the diagnostic workup of hereditary tubulointerstitial disorders not identified after routine genetic testing.

IgG4-related kidney disease: Clinicopathologic features, differential diagnosis, and mimics.

IgG4-related kidney disease (IgG4-RKD) encompasses all forms of kidney disease that are part of IgG4-related disease (IgG4-RD). First recognized as IgG4-related tubulointerstitial nephritis (IgG4-TIN), and then IgG4-related membranous glomerulonephritis (IgG4-MGN), we now recognize additional patterns of interstitial nephritis, glomerular disease, and vascular disease that can be seen as part of IgG4-RKD. The clinical presentation is variable and can include acute or chronic kidney injury, proteinuria or nephrotic syndrome, mass lesion(s), and obstruction. While usually associated with other organ involvement by IgG4-RD, kidney-alone involvement is present in approximately 20 % of IgG4-RKD. Compared to IgG4-RD overall, patients with IgG4-RKD are more likely to show increased serum IgG4 or IgG, and more likely to have hypocomplementemia. In this review, we extensively cover other types of autoimmune and plasma cell-rich interstitial nephritis, mass forming inflammatory diseases of the kidney, and other mimics of IgG4-TIN, in particular ANCA-associated disease.

PLA2R-positive membranous nephropathy in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder associated with IgG4-RD, but membranous nephropathy is also seen in some cases. CASE PRESENTATION: Herein we report on the case of a 77-year-old male patient with nephrotic syndrome and IgG4-related lung disease. His serum phospholipase A2 receptor (PLA2R) antibody was positive. His renal biopsy specimen was also positive for PLA2R. The renal biopsy specimen showed membranous nephropathy with equal IgG3 and IgG4 immunofluorescence staining and no interstitial nephritis, suggesting IgG4-RD manifesting as membranous nephropathy. CONCLUSIONS: Nephrotic syndrome caused by membranous nephropathy is sometimes associated with IgG4-RD. In such cases, even if serum PLA2R antibody is positive, it should be considered that the membranous nephropathy may be secondary to IgG4-RD.

Nephrotic syndrome with acute kidney injury due to combination therapy of immune checkpoint inhibitors: a case report and review of the literature.

BACKGROUND: Recent studies have focused on immune checkpoint inhibitors. Renal complications associated with the use of immune checkpoint inhibitors are uncommon compared with other immune-related adverse events. Acute interstitial nephritis accounts for most of these renal complications, with nephrotic syndrome quite rare. We herein report a case of nephrotic syndrome associated with immune checkpoint inhibitors that was more severe than that in previous cases. By comparing this case with previous reports, the possible reasons for the particular severity of this case are discussed. CASE PRESENTATION: A 75-year-old man developed nephrotic syndrome with acute kidney injury after the first combination therapy of nivolumab and ipilimumab for malignant pleural mesothelioma. The results of a kidney biopsy indicated minimal change disease with mild atherosclerosis, acute interstitial nephritis, and fusion of nearly all podocyte foot processes. Nivolumab and ipilimumab therapy were stopped, and treatment with corticosteroids was initiated. We investigated previously reported cases of nephrotic syndrome using immune checkpoint inhibitors. Seventeen cases of immune checkpoint inhibitor-related nephrotic syndrome, including ours, have been reported. Two of the 17 patients with immune checkpoint inhibitor-related nephrotic syndrome required hemodialysis treatment for acute kidney injury. Unlike many previously reported cases, the present patient was administered two different immune checkpoint inhibitors, which may be one of the reasons for the development of severe nephrotic syndrome. CONCLUSIONS: In addition to previously reported risk factors, immune checkpoint inhibitor combination therapy can exacerbate nephrotic syndrome compared to immune checkpoint inhibitor monotherapy.

Treatment of BK Polyomavirus-Associated Nephropathy in Paediatric Kidney Transplant Recipients: Leflunomide Versus Cidofovir.

OBJECTIVES: BK polyomavirus-associated nephropathy is a clinicopathological entity that negatively affects graft function in kidney transplant recipients. We compared the efficacy of leflunomide and cidofovir to treat BK polyomavirus-associated nephropathy in pediatric kidney transplant recipients. MATERIALS AND METHODS: Medical records of pediatric recipients with BK viremia for the period 2004 through 2019 were reviewed retrospectively, and patients diagnosed with BK polyomavirusassociated nephro-pathy were included in the study. A serum BK virus level above 104 copies/mL was accepted as BK viremia. We defined BK polyomavirusassociated nephropathy as detection of BK virus SV40 antigen on immunochemistry staining of renal graft tissue accompanied by signs of tubulointerstitial nephritis or elevated serum creatinine in addition to BK viremia. RESULTS: Of 304 kidney transplant recipients, 53 had persistent BK viremia; 36 of these patients (61.1% male) were included in the study with the diagnosis of BK polyomavirus-associated nephropathy. Twelve patients (33.3%) received cidofovir, and 14 (38.8%) received leflunomide. Results were similar between the cidofovir and leflunomide groups for serum creatinine level at last follow-up (0.91 ± 0.29 vs 0.94 ± 0.37 mg/dL, respectively; P = .843) and graft failure rate (8.3% vs 14.2%, respectively; P = .632). Graft failure was observed in 8.3% of patients with BK polyomavirus-associated nephropathy. CONCLUSIONS: Leflunomide and cidofovir showed similar efficacy for treatment of BK polyomavirus-associated nephropathy.

Multiple myeloma presenting as acute tubulointerstitial nephritis

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

Hemoptisis recurrente asociada a falla renal y hematuria: otra de las mil caras de la enfermedad relacionada a IgG4 / IgG4 associated nephritis and recurrent hemoptysis: case report

IgG4 disease is a multi-systemic condition involving pancreas, salivary glands and lymph nodes. Less frequently, it causes interstitial nephritis and involves the lungs. We report a 58 years old male with a four years history of hemoptysis and renal dysfunction characterized by hematuria and proteinuria, responsive to steroidal therapy. The renal biopsy established the diagnosis of IgG4 associated interstitial nephritis. Lung involvement was considered secondary to the same systemic disease.

Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease / Nefrite túbulo-intersticial aguda com insuficiência renal grave associada à doença multissistêmica por IgG4

Abstract The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients.

Resumo A doença relacionada à IgG4 tem um espectro clínico amplo em que múltiplos órgãos podem ser afetados, e o diagnóstico depende de achados histopatológicos típicos e elevada expressão de IgG4 em plasmócitos no tecido afetado. Descrevemos o quadro clínico e a evolução de um paciente com nefrite túbulo-intersticial aguda, insuficiência renal grave e manifestações sistêmicas como linfoadenomegalias e pancreatite crônica. O diagnóstico foi confirmado pelas características clínicas e pela histopatologia renal e de linfonodo, na qual a imunohistoquímica mostrou tecido linfoide com policlonalidade e expressão aumentada de IgG4, com uma relação IgG4/IgG total > 80%. O paciente foi tratado com prednisona na dose de 60 mg/dia, seguido de micofenolato mofetil, e apresentou melhora clínica e da função renal depois de 6 meses de tratamento. O alto índice de suspeição da doença relacionada ao IgG4 com comprometimento multissistêmico e o tratamento precoce desta condição são primordiais para a melhora do prognóstico destes pacientes.

Síndrome de nefritis tubulointersticial y uveítis / Interstitial Tubule Nephritis Syndrome and Uveitis

El síndrome de nefritis tubulointersticial y uveítis es una causa infrecuente de disfunción renal aguda en los adultos. El diagnóstico puede hacerse difícil, pues con frecuencia no coinciden temporalmente los síntomas oculares y renales. Se presentaron dos casos de síndrome de nefritis tubulointersticial y uveítis en adultos, con evolución favorable con tratamiento esteroideo sistémico(AU)

Tubulointerstitial nephritis syndrome and uveitis is an uncommon cause of acute renal dysfunction in adults. The diagnosis can be difficult, as ocular and renal symptoms often do not coincide temporarily. Two cases of tubulointerstitial nephritis syndrome and uveitis in adults, with favorable evolution with systemic steroid treatment are presented in this paper(AU)

Síndrome de nefritis túbulo-intersticial agudo asociado a uveítis / Tubulointerstitial nephritis syndrome and uveitis

La uveítis intermedia es una enfermedad ocular caracterizada por la inflamación de la úvea, principalmente el vítreo anterior, la retina periférica y la pars plana. Diversas etiologías de carácter infeccioso, inflamatorio sistémico y local pueden asociarse a dicho fenómeno. Un cuadro infrecuente es el síndrome de nefritis túbulo-intersticial aguda asociado a uveítis. Presentamos el caso de una mujer de 64 años con antecedente de tiroiditis de Hashimoto, que desarrolló pérdida brusca de la agudeza visual en contexto de falla renal aguda. Se trata de una paciente con nefritis túbulo-intersticial aguda asociada a uveítis.

Intermediate uveitis is described as inflammation in the anterior vitreous, ciliary body and the peripheral retina. It is a subset of uveitis where the vitreous is the major site of damage. It has been reported to be associated with many local and systemic inflammatory and infectious diseases. An infrequent cause is the tubulointerstitial nephritis and uveitis syndrome. We report a case of an acute visual acuity loss related with renal failure in a 64 years old woman with Hashimoto disease. It was an acute tubulointerstitial nephritis and uveitis syndrome case.

Relato de caso: nefrite intersticial aguda causada por uso intermitente de rifampicina: dois casos / Relate the cases: acute intersticial nephritis caused by intermiten use of rifampin two cases

A rifampicina (RFP) é um antibiótico largamente utilizado no tratamento de doenças infecciosas. O uso intermitente da droga ocasiona vários efeitos colaterais, entre eles insuficiência renal aguda (IRA). Säo relatados dois casos de pacientes portadores de hanseníase que após o uso intermitente de RFP evoluíram para IRA, anemia hemolítica e hepatotoxidade. Säo revistos os principais mecanismos causadores da IRA, sua evoluçäo e tratamento (au)

Síndrome nefritis intersticial aguda y uveítis / Interstitial nephritis syndrome and uveitis

Un niño de 9 años ingresó al hospital por anemia severa (hematocrito 18%) y enrojecimiento del ojo derecho, comprobándose en oftalmología que sufría uveítis. La velocidad de sedimentación de los eritrocitos (VHS) era 101 mm * h, ureico 91 mg/dl, depuración plasmática de creatinina 9 ml/min * 1,73 m*, concentraciones séricas de IgG e IgM 2.368 mg/dl y 263 mg/dl respectivamente, sobre los márgenes normales para su edad, con IgA apenas detectable y reducción de las poblaciones de células T. Los ensayos de factor reumatoide, anticuerpos antinucleares y antimúsculo liso dieron resultados negativos. Las actividades de las fracciones C3 y C4 del complemento sérico y el sedimento de orina eran normales. La muestra de la biopsia renal incluía 25 glomérulos, uno totalmente esclerótico, dos con fibrosis periglomerular y los restantes sólo con leve aumento de la matriz mesangial. Había, además, intensa infiltración inflamatoria del intersticio, con estructuras granulomatosas que incluían células gigantes, semejantes observables en reacciones por cuerpos extraños, y cristales PAS positivos en el interior de los lúmenes tubulares. A pesar del empleo de tratamiento esteroidal, el que se complicó al final con un granuloma inflamatorio intracerebral que curó en coincidencia con el uso de antibióticos por vía parenteral, el paciente evolucionó hacia la insuficiencia renal crónica y actualmente está siendo sometido a hemodiálisis, con perspectivas de transplante renal. La uveítis fue tratada con colirios de atropina y esteroides, curando con secuelas mínimas

Mecanismos de esclerose glomerular / Mecanisms of glomerular sclerosis

O desenvolvimento da esclerose glomerular e a deterioraçäo progressiva da funçäo renal säo características comuns a todas as nefropatias que evoluem para o estado terminal. Os autores descrevem e analisam criticamente as principais teorias propostas para explicar a natureza progressiva das lesöes renais, quais sejam: teoria hemodinâmica, o comprometimento túbulo-intersticial, a deposiçäo glomerular de lípides, a hipertrofia glomerular e o papel dos prostanóides

Envolvimento renal na endocardite bacteriana / Renal invalvement in bacterial endocarditis

Com o objetivo de estudar o envolvimento renal na endocardite bacteriana em nosso meio, foram retrospectivamente estudados 47 pacientes necropsiados no Hospital Professor Edgard Santos, UFBA. O óbito esteve relacionado ao processo infeccioso em 2/3 dos pacientes, seguido pelos fenômenos trombembólicos; insuficiência cardíaca congestiva esteve associada, na maioria. Ao estudo anatomopatológico, os infartos renais e microabscessos foram os encontros mais freqüentes; glomerulonefrites proliferativas foram documentadas em dez pacientes e nefrite intersticial em três. Anormalidade do exame sumário de urina estiveram presentes em 74% dos pacientes e insuficiência renal, geralmente leve a moderada, em 53%. Em nenhum pacientes a urina foi considerada a causa do óbito. Embora todos os pacientes nos quais se documentou, histologicamente, glomerulopatia apresentassem alteraçöes do exame sumário de urina, näo houve correlaçäo com a funçäo renal. O envolvimento renal na endocardite bacteriana näo é infreqüente; a insuficiência renal, é geralmente, leve a moderada, multifatorial, porém freqüentemente relacionada a fatores hemodinâmicos e ao uso de nefrotóxicos