|Year : 2020 | Volume
| Issue : 2 | Page : 78-81
Clinicopathological spectrum and outcome of rapidly progressive glomerulonephritis
Gulshan Nigar Chaudhury1, Tarannum Khandoker1, Tahmina Ferdous1, Rifat Asma Chowdhury2, Shireen Afroz3, Mohammed Hanif1
1 Department of Pediatric Nephrology, Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh
2 Department of Microbiology, Shahid Suhrawardy Medical College and Hospital, Dhaka, Bangladesh
3 Department of 2Critical Care Nephrology, Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh
|Date of Submission||05-Sep-2020|
|Date of Decision||09-Oct-2020|
|Date of Acceptance||09-Dec-2020|
|Date of Web Publication||31-Dec-2020|
Gulshan Nigar Chaudhury
Department of Pediatric Nephrology, Dhaka Shishu (Children) Hospital, Dhaka
Source of Support: None, Conflict of Interest: None
Rapidly progressive glomerulhronephritis (RPGN) is a severe condition characterized by rapid loss of kidney function which is irreversible if not diagnosed and treated promptly. This study analyzed the etiology, histopathology, clinical course, treatment pattern, and prognosis of RPGN in 25 children presenting to the Department of Pediatric Nephrology in Dhaka Shishu (Children) Hospital between June 2017 and December 2019. All patients had proteinuria and edema, and presented with serum creatinine of 5.82 ± 4.27 mg/dL; 14 (56%) required renal replacement therapy. Immune-complex glomerulonephritis (GN) was the principal histological category, of which IgA nephropathy (28%) and postinfectious GN (24%) were the predominant etiology. No patients had pauci-immune or anti-glomerular basement membrane GN. Glomeruli displayed cellular crescent in 24% cases, fibrous in 8%, and fibrocellular in 40% biopsies. Interstitial fibrosis and tubular atrophy were present in 4% and 36% biopsies, respectively. Therapy for induction included intravenous (IV) methylprednisolone in all patients, IV cyclophosphamide in 36% cases and mycophenolate mofetil in 52% patients. While 15 patients recovered renal function completely, two each were dialysis-dependent and developed progressive chronic kidney disease; 3 died during hospital stay and 5 patients were lost to follow-up. RPGN is chiefly secondary to immune-complex-mediated GN in developing countries and is associated with adverse outcomes in a high proportion of cases, underscoring the need for prompt evaluation and aggressive management.
Keywords: Acute kidney injury, children, crescentic glomerulonephritis, kidney failure
|How to cite this article:|
Chaudhury GN, Khandoker T, Ferdous T, Chowdhury RA, Afroz S, Hanif M. Clinicopathological spectrum and outcome of rapidly progressive glomerulonephritis. Asian J Pediatr Nephrol 2020;3:78-81
|How to cite this URL:|
Chaudhury GN, Khandoker T, Ferdous T, Chowdhury RA, Afroz S, Hanif M. Clinicopathological spectrum and outcome of rapidly progressive glomerulonephritis. Asian J Pediatr Nephrol [serial online] 2020 [cited 2021 Jan 23];3:78-81. Available from: https://www.ajpn-online.org/text.asp?2020/3/2/78/305923
| Introduction|| |
Rapidly progressive glomerulonephritis (RPGN), characterized by an acute nephritic illness with rapid loss of renal function over days to weeks, is the syndrome typically associated histologically with crescentic glomerulonephritis (GN)., The diagnosis of crescentic GN is based on demonstration of crescents of epithelial cells in Bowman space, involving more than 50% glomeruli. Based on histology and immunofluorescence staining, three types of crescentic GN are recognized: Immune complex, pauci-immune and anti-glomerular basement membrane (GBM) GN. The most common pattern of crescentic GN in children is immune complex GN., RPGN is a diagnostic as well as therapeutic emergency. Information on etiology and outcomes of crescentic GN in children from developing countries is limited. This study evaluated the clinical characteristics, etiology, histomorphological parameters, and prognosis of pediatric patients presenting with RPGN at one center in a developing country.
| Methods|| |
We report the course and outcomes of all children (<18-year-old) presenting with RPGN at the Department of Pediatric Nephrology, Dhaka Shishu (Children) Hospital from June 2017 to December 2019. The study was approved by the local ethics committee and informed consent was taken from the parents and/or patients.
Clinical and demographic parameters at first visit were recorded, along with key biochemical parameters and results of immunological investigations, including levels of complement C3 and C4, anti-streptolysin O, anti-nuclear antibodies, anti-double stranded deoxyribonucleic antibodies, anti-neutrophilic cytoplasmic antibodies performed in all patients to determine etiology.
Kidney biopsy was performed in all patients but was delayed to 1–2 weeks after admission if the patient was clinically unstable. Light microscopy was performed on kidney tissue samples fixed in 10% formaldehyde. The presence of large epithelial crescents involving 50% or more glomeruli was considered diagnostic of crescentic GN. Immunofluorescence staining for IgA, IgG, IgM, C3, CIq, and fibrinogen were performed.. Electron microscopy was not performed due to lack of facility for the same at the center.
All patients presenting with RPGN and histological diagnosis of GN with crescents were included; unlike other studies, we did not exclude patients with fewer than 50% crescents. Patients with chronic kidney disease were excluded. Records of therapy were noted, including antihypertensive and immunosuppressive agents and supportive care, including the need for kidney replacement therapy. Outcome at the end of 3 months' follow-up is reported.
| Results|| |
[Table 1] reports baseline characteristics of the 25 patients included in the study, with a preponderance (68%) of boys and median age 10.2 (range 3.5–16) years. Most patients were symptomatic for 2–3 weeks, and all had edema and proteinuria. Investigations are summarized in [Table 1]. None of the patients had infection with hepatitis B or C. Most patients had immune-complex GN, of which IgA nephropathy (28%) and postinfectious GN (24%) were the predominant etiology [Figure 1]. Histological findings are summarized in [Table 2]. None of the patients had pauci-immune or anti-GBM GN.
|Figure 1: Etiology of rapidly progressive glomerulonephritis. Numbers of patients are placed next to the pie slices. C1q C1q nephropathy; C3 C3 glomerulonephritis. DPGN: Diffuse proliferative glomerulonephritis, HSP: Henoch Schonlein purpura, IE: Infective endocarditis, MPGN: Membranoproliferative glomerulonephritis, PIGN: Postinfectious glomerulonephritis|
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Fourteen (56%) patients required dialysis at presentation. None of the patients underwent therapeutic apheresis. Induction immunosuppression comprised of IV methylprednisolone in all patients, often initiated prior to biopsy, followed by IV cyclophosphamide in 9 (36%) patients and mycophenolate mofetil (MMF) in 13 (52%) patients. Maintenance immunosuppression included oral prednisolone and MMF. Antihypertensive agents were administered to 19 (76%) patients. Outcomes at 3-month follow-up are listed in [Table 3].
| Discussion|| |
We report the clinical and histological findings in 25 patients presenting with RPGN at a teruary care center in Bangladesh. Most patients with RPGN presented to our center following initial management at local health centers or by traditional healers, leading to delayed diagnosis and management. The preponderance of boys in our study is similar to findings in a report from north India. In contrast, a study from Saudi Arabia reported a higher proportion of girls (57.5%) than boys, possibly to a higher proportion of cases with underlying systemic lupus erythematosus. Almost all patients had severe disease at presentation, with need for dialysis in the majority of patients, similar to another series. Proteinuria and hematuria were universal, as is also reported by Brown, et al. and three-fourth of children had hypertension and edema, similar to a report from south India that reported edema, hematuria, and hypertension in 75%, 60%, and 40% patients, respectively.
Immune-complex GN constituted the chief etiology of crescentic GN, within which IgA nephropathy and postinfectious GN were the predominant categories, similar to other series.,,, An Indian study reported IgA nephropathy as the most frequent etiology, followed by lupus nephritis and postinfectious GN. In contrast, lupus nephritis preceded pauci-immune GN and IgA nephropathy as the most cause of crescentic GN in a study from China. Two studies from Saudi Arabia and sub-Saharan Africa also found lupus as the predominant cause, followed by PIGN. The high incidence of lupus in these studies might be due to racial or ethnic predisposition.
The current study revealed fibrocellular crescents as the predominant crescentic type, similar to the findings of Choudhury et al. The proportion with cellular and fibrous crescents were 24% and 8%, respectively, close to the findings of El-Hussein et al..
The severity of disease at presentation is indicated by the need for dialysis in more than half the patients in our series. This proportion is comparable to that reported in 4 other series from south Asia.,,, While 60% patients in our study achieved remission, the overall prognosis is not satisfactory, similar to that reported in series from across the world.,,,,,,,,,,,, The severity of renal insufficiency at presentation is an important predictor of outcomes in follow-up; other factors reported to be associated with adverse outcomes in pediatric patients with crescentic GN include etiology of disease, high (>80%) proportion of glomeruli with crescents, and presence of histologic features suggesting chronicity, such as fibrous crescents and tubulointerstitial fibrosis. Despite prompt institution of immunosuppression at presentation to our center and adequate supportive care, including dialytic support, renal recovery was incomplete, most likely due to delayed referral and severe disease at presentation.
Rapidly progressive GN is among the most important etiology of severe acute kidney injury. Severe renal insufficiency on admission, frequent irreversible loss of renal function and high mortality highlight the need to increase awareness about crescentic GN to enable early referral and specific management.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]