CJASN Covers
Since the inaugural issue in 2006, CJASN has featured visually engaging images on its covers. Cover images are submitted by authors and undergo peer review to ensure they are of high quality. To submit a cover image submission, please see the CJASN Instructions for Authors.
Check out this year's covers:
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March 2023
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February 2023
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January 2023
March 2023
What is the diagnosis?
A 44-year-old man with a 10-cm left kidney mass underwent a laparoscopic left radical nephrectomy. His serum creatinine was 1.7 mg/dl, and he had trace proteinuria after surgery.
Image Description:
The histopathology revealed clear cell renal cell carcinoma, histologic grade 3, and stage pT3aN0M1. Immunohistochemistry on the tumor showed diffuse PAX8 nuclear positivity. Histopathological examination of the non-neoplastic kidney revealed intracapillary seeding of tumor cellswith the morphology of clear cell renal cell carcinomawithin some glomeruli. Immunohistochemistry for PAX8 showed nuclear positivity in these tumor cells. PAX8 is a transcription factor expressed in renal epithelial cells and is a marker for primary and metastatic renal carcinomas. PAX8 positivity in the glomerular intracapillary tumor cells differentiated them from the native cells of the glomerular tuft and established its renal tubular epithelial origin.
Teaching Points:
Despite constantly filtering blood, the glomerulus is a very rare site for metastatic tumor deposits. Intraglomerular metastasis is characterized by the seeding ofmalignant cells in the glomerulus, which can occurwithin the glomerular tuft (intracapillary) or in the Bowman’s space (extracapillary) as tumor crescents. Most cases of intraglomerular metastasis were reported in autopsy studies and had their origin from lung, breast, thyroid, ovarian, and pancreatic carcinomas. Intraglomerular metastasis from ipsilateral clear cell renal cell carcinoma is extremely rare. Kidney metastases mostly involve the tubulointerstitial compartment and are very rarely seen within glomeruli. Invasion of the tumor cells into the renal vein and dissemination into systemic circulation followed by intraglomerular seeding is the most likely event in our patient. Immunohistochemistry plays an important role in correct diagnosis. Careful examination of the non-neoplastic renal cortex in all nephrectomies is recommended because this entity is a manifestation of a widely disseminated disease.
Reference
1. Carr RA, Yoong AK, Newman J. Intracapillary glomerular metastases in a nephrectomy specimen removed for ipsilateral renal cell carcinoma. J Clin Pathol. 1994;47(6):558-559. doi:10.1136/jcp.47.6.558
Images and text provided by Malathi Navinath, Renopath, Center for Renal and Urological Pathology, Chennai, India; Arun Kumar Balakrishnan, Asian Institute of Nephrology and Urology, Chennai, India; Venkat Subramaniam Dhandapani, Asian Institute of Nephrology and Urology, Chennai, India; and Anila Abraham Kurien, Renopath, Center for Renal and Urological Pathology, Chennai, India
February 2023
What is the Diagnosis?
A 67-year-old male started hemodialysis in 1999 due to glomerulonephritis. He underwent a kidney transplant in 2004, which failed in 2009, leading to a return to dialysis. He is receiving 4-hour postdilution hemodiafiltration thrice weekly, presently with a polyester polymer alloy membrane, a well-functioning arteriovenous fistula, and an average Kt/V in the last 2 years equal to 1.3. He is compliant with his dialysis treatments and medical prescriptions and is waitlisted for a kidney graft, but a high anti-HLA antibody titer reduces his chances of undergoing a second transplantation. He underwent surgery for carpal tunnel syndrome in 2013 and 2014, raising concerns for dialysis-related amyloidosis (DRA). He also started to complain about cervical pain and dysesthesia of upper limbs, so a magnetic resonance imaging (MRI) and positron emission tomography (PET) scan were performed to search for amyloid deposits.
Image Description:
The images show a severe complication of DRA, called destructive spondiloarthropathy (DSA). Radiograms show narrowing of the intervertebral spaces and irregular bone erosions; the lesions are more evident at MRI (narrowing of the intervertebral spaces, with erosions of the adjacent vertebral endplates, in the absence of osteophytes, with low signal intensity at the intervertebral disc space on T1- and T2-weighted images, left image). PET scan (top right image) shows a moderate increase in metabolic activity in keeping with active inflammation favoring further beta2-microglobulin amyloid deposition in the spine and shoulder (bottom right image). The patient was already treated by high-efficiency hemodiafiltration, known to have the best removal of B2 microglobulin; the room for optimization of the dialysis procedure was limited, the patient did not want to increase dialysis frequency, and we added doxycycline according to the suggestions of Montagna and coworkers.1,2
Teaching Points:
DSA, a severe form of DRA, is caused by beta2-microglobulin amyloid deposition in the intervertebral discs, leading to inflammation and progressive replacement of normal tissue by amyloid deposits of beta2-microglobulin amyloid.2,3 The risk increases with exposure to KRT and aging, and inflammation may be reduced, but not offset, by biocompatible dialysis membranes, high flux hemodiafiltration, and ultrapure water. DRA usually involves multiple joints and is a frequent cause of carpal tunnel syndrome in dialysis patients, whereas DSA may occur along the entire spine, with variable intensity and progression rate. There are no definitive imaging studies, and the diagnosis should rely on imaging and clinical features and the medical history of the patient.
There is no treatment for DSA, but successful kidney transplantation may stop its evolution. The neurologic deficits may be severe enough to require surgical interventions. Awareness of these severe lesions can guide diagnosis and multidisciplinary follow-up.
References
1. Montagna G, CazzulaniB,Obici L, et al. Benefit ofdoxycycline treatment on articular disability caused bydialysis relatedamyloidosis. Amyloid. 2013;20:173-178. doi:10.3109/13506129.2013.803463
2. Hoshino J, Yamagata K, Nishi S, et al. Significance of the decreased risk of dialysis related amyloidosis now proven by results from Japanese nationwide surveys in 1998 and 2010. Nephrol Dial Transplant. 2016;31:595-602. doi:10.1093/ndt/gfv276
3. Hayami N, Hoshino J, Suwabe T, et al. Destructive spondyloarthropathy in patients on long-termperitoneal dialysis or hemodialysis. Ther Apher Dial. 2015;19:393-398. doi:10.1111/1744-9987.12282
Images and text provided by Giorgina Barbara Piccoli, Néphrologie et dialyse, Centre Hospitalier Le Mans, Le Mans, France; Emanuela Cataldo, Néphrologie et dialyse, Centre Hospitalier LeMans, LeMans, France, and Department of Nephrology, University AldoMoro, Bari, Italy; Francesco Lavra, Radiology, Centre Hospitalier Le Mans, Le Mans, France; Massimo Torreggiani, Néphrologie et dialyse, Centre Hospitalier Le Mans, Le Mans, France; and Francesco Cinquantini, Radiology, Centre Hospitalier Le Mans, Le Mans, France.
January 2023
What is the Diagnosis?
A 33-year-old woman was admitted to our institute because of a fever of 39°C, followed by gross hematuria, that occurred 2 days after the second dose of the Pfizer-BioNTech coronavirus 2019 (COVID-19) vaccine. The next day, the urine test identified many red blood cells and protein (>5 g daily). She had been asymptomatic after the first dose of the vaccine. Until then, no abnormalities had been detected with urinalysis, but this patient had been aware of dark urine after common cold symptoms since around 2 years ago, but it was mild compared with the hematuria in the present case. As the gross hematuria persisted, a kidney biopsy was performed 2 weeks later. On admission, the patient was 154.0 cm tall and weighed 54.1 kg; her blood pressure was 128/74 mm Hg. The laboratory findings were as follows: serum creatinine, 0.74 mg/dl; estimated glomerular filtration rate, 73 ml/min per 1.73 m2; C-reactive protein, 0.07 mg/dl; immunoglobulin G (IgG), 943 mg/dl normal range, 860–1740 mg/dl); and IgA, 303 mg/dl (normal range, 93–393 mg/dl). The 24-hour urinary protein excretion was 2.03 g, and the urine sediment contained 30–49 red cells per high-power field. No red blood cell casts were found.
Image Description:
Light microscopy of a kidney biopsy specimen showed global sclerosis in seven out of 41 glomeruli. Mesangial and endocapillary hypercellularity and segmental scar were also seen. Periodic acid-Schiff (PAS staining) showed cellular crescent (arrow) (left image). Periodic acid-methenamine silver (PAM staining) showed fibrocellular crescent (arrow) (middle image). Definite fibrinoid necrosis was not found. Tubulointerstitial fibrosis in the cortical area was about 15%. Immunofluorescence study showed 21 finely granular mesangial positive staining for IgA (arrow) (right image). Electron microscopy showed electron dense deposits in the mesangial region. According to the Oxford classification, MEST-C scores were M1, E1, S1, C1, and T0.
Treatment was started with three weekly cycles of methylprednisone pulse therapy (500 mg/d for 3 days), followed by oral prednisolone at 30 mg every other day, but gross hematuria persisted. Forty days later, bilateral tonsillectomy was performed. Immediately after the operation, the gross hematuria improved and became microscopic hematuria, and after 100 days the microscopic hematuria also disappeared. Nine months after kidney biopsy, serum creatinine was 0.60 mg/dl; urinary protein excretion, 0.01 g daily; the urine sediment, <1 red cells per high-power field. Prednisolone are reduced by 5 mg every 2 months.
Teaching Points:
We made a diagnosis of IgA nephropathy with cellular crescents manifesting after vaccine. Cellular crescent formation in cases with IgA nephropathy has been noted as an indicator of severe disease. There have been reports of patients with IgA nephropathy with worsening urinary findings, such as gross hematuria, after COVID-19 vaccine, but many of these cases are known to spontaneously remit. We report here on a case of persistent gross hematuria in a severe case of IgA nephropathy with crescent formation, in which it has been reported that hematuria only occurs after the onset of a high fever following vaccine administration in patients with IgA nephropathy but whose disease has become quiescent, and there have also been reports of new development cases of the disease. Our patient was considered to be a probable reactivation of preexisting disease, because she had a past history of dark urine after common cold symptoms and many glomeruli of global sclerosis on kidney biopsy. The mechanism of exacerbation of IgA nephropathy after vaccine administration is not fully understood; however, the following mechanisms can be inferred from a review of previous reports. Many cases have developed or recurred in cases with underlying diseases originally associated with immune abnormalities, characterized by a high incidence of onset after the second vaccine administration—IgA nephropathy is the most common. This indicates that IgA nephropathy is a disease associated with immune abnormalities. Higher immunogenicity produced by this vaccine leads to treatment against COVID-19 viruses, but it could lead to unexpected and perhaps nonspecific immune activation. It is likely that this underlying immune dysregulation is a risk factor for development of IgA nephropathy or exacerbation of this disease.
Images and text provided by Wasako Tato, Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan; Hiroki Mizuno, Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan; Naoki Sawa, Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan, and Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan; and Yoshifumi Ubara, Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan, and Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
