| Abstract|| |
A 14-year-old female presented with oliguric dialysis requiring kidney injury due to acute poststreptococcal glomerulonephritis (PSGN) with hypertension strongly suggestive of atypical hemolytic uremic syndrome (aHUS) with microangiopathic hemolytic anemia and elevated factor H antibody levels. Renal biopsy revealed crescentic glomerulonephritis with typical subepithelial, intramembranous and mesangial electron-dense deposits (humps) on electron microscopy. She was treated with glucocorticoids following which she recovered, remained dialysis free and her Factor H antibody levels and depressed complement 3 levels normalized. PSGN-associated HUS has rarely been described, with this patient being the 11th case reported, to the best of our knowledge. This case is unique as we describe the course and management of the first patient with PSGN-associated HUS in the era of eculizumab, without eculizumab, and plasmapheresis. This patient presented with clinical and histological features of PSGN as well as anemia and thrombocytopenia consistent with aHUS. Given that these diseases are both mediated through the alternate complement pathway, it is tempting to speculate that blockade of the terminal complement pathway through the use of eculizumab might improve outcomes. Temporally, the hematological parameters in our patient seemed to improve soon after treatment was initiated; however, none of the prior cases in the literature experienced any long-term hematological issues, suggesting that supportive management can be a reasonable alternative.
|How to cite this article:|
Parekh M, Konnur A, Gang S. Poststreptococcal glomerulonephritis with atypical hemolytic uremic syndrome: An unusual presentation. Saudi J Kidney Dis Transpl 2018;29:728-31
|How to cite this URL:|
Parekh M, Konnur A, Gang S. Poststreptococcal glomerulonephritis with atypical hemolytic uremic syndrome: An unusual presentation. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2022 Jan 28];29:728-31. Available from: https://www.sjkdt.org/text.asp?2018/29/3/728/235201
| Introduction|| |
Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. About 90% of cases occur following a diarrheal illness with Shiga-like toxin-producing bacteria and the remaining 10% fall into the category of atypical HUS (aHUS), which consists of a heterogeneous group of disorders with 50%-60% of cases being associated with either genetic or antibody-mediated complement dysregulation. Usually, children with the aHUS phenotype have a more favorable prognosis, may not have associated complement dysregulation and may not require treatment with plasmapheresis or anti-C5 antibody (eculizumab).,
Poststreptococcal glomerulonephritis (PSGN) is the most common cause of glomerulonephritis in children, presenting one to three weeks after streptococcal infection, and is usually associated with depressed C3 levels for up to eight weeks.
In 1980, de Chadarévian et al first described the simultaneous occurrence of acute PSGN and HUS. There have been at least 10 cases describing aHUS associated with PSGN in the literature.,,,,,,, Importantly, these cases fall under the category of aHUS, as they are not associated with diarrhea or Shiga toxin exposure. Only three of these cases showed thrombotic microangiopathy on renal biopsy.,,
| Case Report|| |
Written informed consent was obtained from the family of the patient before reporting the case. A 14-year-old female presented with two weeks history of progressive facial edema, pedal edema, oligoanuria, and cola colored urine. Two weeks before, she had a history of fever, low grade with cough and sore throat. She had no history of bloody diarrhea or rash.
On admission to Muljibhai Patel Urological Hospital, her blood pressure was 116/70 mm Hg with no postural drop. Physical examination revealed facial edema and bilateral lower extremity pitting edema along with crepitations in the lower zones of both lungs. Urinalysis demonstrated 4+ protein and a large amount of blood with numerous red blood cell casts. Initial blood workup demonstrated a creatinine of 12.83 mg/dL, potassium 5 mmol/ L, albumin 2.8 g/dL, hemoglobin 6 g/dL, platelet count 94,000/μL, lactate dehydro genase 919 units/L, anti-streptolysin O (ASO) titer >200 IU/mL, C3 29.7 mg/dL, and C4 0.21 (0.1-0.4) g/L along with peripheral smear showing plenty of schistocytes. Owing to oliguric acute kidney injury with acidosis and fluid overload, she was started on dialysis and underwent a renal biopsy [Figure 1],[Figure 2],[Figure 3].
|Figure 1: Glomeruli showed moderate mesangial proliferation with neutrophilic exudation and partial obliteration of capillary lumina. Basement membrane shows thickening and focal reduplication. Interstitium showed mild-to-moderate edema, and patchy cell infiltrate. Tubules showed focal dilatation. No fibrin thrombi were identified. Blood vessels were largely unremarkable.|
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|Figure 2: Immunofluorescence revealed 2+ coarse granular IgG staining (primarily in the mesangium), 3+ coarse granular C3 staining (in the mesangium and capillary loops) and +1 coarse granular staining of IgA.|
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|Figure 3: Subepithelial and more numerous intramembranous and mesangial electron-dense deposits (humps) were observed on electron microscopy.|
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42/63 glomeruli show partial to complete encircling cellular crescents. The glomeruli showed moderate mesangial proliferation with neutrophilic exudation and partial obliteration of capillary lumina. Basement membrane showed thickening and focal reduplication. The interstitium showed mild-to-moderate edema and patchy cell infiltrate. Tubules showed focal dilatation.
No fibrin thrombi were identified. Blood vessels were largely unremarkable.
Immunofluorescence revealed 2+ coarse granular IgG staining (primarily in the mesangium), 3+ coarse granular C3 staining (in the mesangium and capillary loops), and +1 coarse granular staining of IgA.
Subepithelial and more numerous intramem branous and mesangial electron-dense deposits (humps) were observed on electron microscopy.
The patient was initiated on hemodialysis. She was ultrafiltrated. In response to her dialysis dependence and crescentic glomerulo nephritis, she was treated with intravenous methylprednisolone 500 mg for three days and subsequently treated with oral prednisone with tapering doses. The oliguria persisted for one week, following which she started showing improvement in urine output of around 1-1.5 L/day along with decreasing edema.
Evaluation for aHUS revealed factor H autoantibodies levels of 209 IU. Her creatinine showed downward trend from 12 to 1.65 over a span of 15 days without dialysis, her platelet counts also improved to 1.53 lakhs with hemoglobin remaining stable at 8.5; her C3 levels also improved to 36.6. The anti-nuclear antibodies were negative along with negative Coombs test, and her peripheral smear also showed only occasional schistocytes on follow-up. Only 10% of patients with aHUS have anti-factor H antibodies (positive in our patient), which respond to plasma exchange alone without plasma infusions, however owing to improving trends of both clinical and laboratory parameters, we selected to continue on steroids only.
At one-month of follow-up, the patient had normal renal function (creatinine 1.02 mg/dL) and +2 proteinuria. Her hemoglobin and platelet count had normalized. The complement levels were rechecked six weeks after initial presentation and had returned to normal (C3, 129 mg/dL.) with ASO titer was <200.
| Discussion|| |
PSGN-associated HUS has rarely been described, with this patient being the 11th case reported. This case is unique as we describe the course and management of the first patient with PSGN-associated HUS in the era of eculizumab and without eculizumab and plasmapheresis.
Usually, the prognosis of PSGN-associated HUS has been favorable, with the majority of patients recovering fully or having mild residual chronic kidney disease or proteinuria.,,,,,,,
Mutations in the factor H gene have been described in patients with aHUS as well as C3 glomerulonephritis.
Interestingly, the histological characteristics of PSGN can be indistinguishable from C3 glomerulonephritis. However, on immunofluorescence, biopsies of patients with C3 glomerulonephritis show isolated C3 staining and are immunoglobulin negative.
Our patient presented with clinical and histo-logical features of PSGN as well as anemia and thrombocytopenia consistent with aHUS. Given that these diseases are both mediated through the alternate complement pathway, it is tempting to speculate that blockade of the terminal complement pathway through the use of eculizumab might improve outcomes.
Temporally, the hematological parameters in our patient seemed to improve soon after treatment was initiated; however, none of the prior cases in the literature experienced any long-term hematological issues, suggesting that supportive management can be a reasonable alternative.
Conflict of interest: None declared.
| References|| |
Caprioli J, Noris M, Brioschi S, et al. Genetics of HUS: The impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood 2006;108: 1267-79.
Ruebner RL, Kaplan BS, Copelovitch L. A time for reappraisal of “atypical” hemolytic uremic syndrome: Should all patients be treated the same? Eur J Pediatr 2012;171: 1519-25.
Neuhaus TJ, Calonder S, Leumann EP. Heterogeneity of atypical haemolytic uraemic syndromes. Arch Dis Child 1997;76:518-21.
Eison TM, Ault BH, Jones DP, Chesney RW, Wyatt RJ. Post-streptococcal acute glomerulonephritis in children: Clinical features and pathogenesis. Pediatr Nephrol 2011;26:165-80.
de Chadarévian JP, Goodyer PR, Kaplan BS. Acute glomerulonephritis and hemolytic uremic syndrome. Can Med Assoc J 1980;123:391-4.
Izumi T, Hyodo T, Kikuchi Y, et al. An adult with acute poststreptococcal glomerulonephritis complicated by hemolytic uremic syndrome and nephrotic syndrome. Am J Kidney Dis 2005;46:e59-63.
Medani CR, Pearl PL, Hall-Craggs M. Acute renal failure, hemolytic anemia, and thrombocytopenia in poststreptococcal glomerulonephritis. South Med J 1987;80:370-3.
Duvic C, Desramé J, Hérody M, Nédélec G. Acute poststreptococcal glomerulonephritis associated with thrombotic microangiopathy in an adult. Clin Nephrol 2000;54:169-73.
Laube G, Sarkissian A, Hailemariam S, Neuhaus TJ, Leumann E. Simultaneous occurrence of the haemolytic uraemic syndrome and acute post-infectious glomerulonephritis. Eur J Pediatr 2001;160:173-6.
Tan PH, Yadin O, Kleinman KS, Gura V, Cohen AH. Simultaneous postinfectious glomerulonephritis and thrombotic microangiopathy: A renal biopsy study. Am J Kidney Dis 1998;31:513-20.
Siebels M, Andrassy K, Waldherr R, Ritz E. Hemolytic uremic syndrome complicating postinfectious glomerulonephritis in the adult. Am J Kidney Dis 1995;25:336-9.
Proesmans W, Baten E, Van Damme B. A boy with acute renal failure. Pediatr Nephrol 1995; 9:389-91.
Bomback AS. Anti-complement therapy for glomerular diseases. Adv Chronic Kidney Dis 2014;21:152-8.
Dr. Abhijit Konnur
Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad - 387 001, Gujarat
[Figure 1], [Figure 2], [Figure 3]