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Pediatrics International (2013) 55, e136–e138
doi: 10.1111/ped.12150
Patient Report
Post-streptococcal acute glomerulonephritis associated with pneumococcal infection Satoshi Hibino,1 Akihiro Hoshino,1 Takanari Fujii,1 Yoshifusa Abe,1 Shuichiro Watanabe,2 Osamu Uemura3 and Kazuo Itabashi1 1 Department of Pediatrics, Showa University School of Medicine, 2Watanabe Children’s Clinic, Tokyo and 3Department of Pediatric Nephrology, Aichi Children’s Health and Medical Center, Aichi, Japan Abstract
Streptococcus pyogenes is the most common cause of post-infectious glomerulonephritis. Described herein is the case of a 5-year-old girl with febrile post-streptococcal acute glomerulonephritis (PSAGN) associated with pneumococcal bacteremia. The chief complaints were fever and macrohematuria without respiratory symptoms. Urinalysis indicated a protein level of 3+. Serological data showed elevated anti-streptolysin O (ASO) and hypocomplementemia. Blood culture was positive for S. pneumoniae. Her acute renal failure was mild and improved over several days. Although PSAGN was confirmed by elevated ASO and transient hypocomplementemia, the clinical course was consistent with those of several reported cases of AGN associated with pneumococcal infection. To our knowledge, there have been few reports on the relationship between pneumococcal infection and the incidence of PSAGN. We suggest the hypothesis that pneumococcal infection itself could exaggerate the complement reaction leading to PSAGN. It is important to consider PSAGN associated with a microbial infection such as S. pneumoniae when faced with a febrile patient with AGN.
Key words pneumococcal infection, post-streptococcal acute glomerulonephritis.
Group A b-hemolytic Streptococcus (GAS), specifically Streptococcus pyogenes, is the most common cause of post-infectious glomerulonephritis. Although other infectious causes are less common, several cases of acute glomerulonephritis (AGN) following infection with S. pneumoniae have been reported.1–7 We report here a pediatric patient with febrile post-streptococcal acute glomerulonephritis (PSAGN) associated with pneumococcal bacteremia. Interestingly, the present clinical course was consistent with those of prior reported cases of AGN associated with pneumococcal infection.1–7 To our knowledge, there have been few reports on the relationship between pneumococcal infection and the incidence of PSAGN. We suggest the hypothesis that pneumococcal infection itself could exaggerate the complement reaction leading to PSAGN.
Case report A 5-year-old Japanese girl was referred to hospital for gross hematuria and fever for 2 days. The findings of physical examination were as follows: body temperature, 39.3°C; pulse rate, 157 beats/min; respiratory rate, 22 breaths/min; and blood pressure, 100/53 mmHg. She had slight palpebral edema and edema of her face and legs bilaterally. The tympanic membrane was
Correspondence: Yoshifusa Abe, MD, PhD, Department of Pediatrics, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawaku, Tokyo 142-8666, Japan. Email: [email protected] Received 19 December 2012; revised 23 April 2013; accepted 31 May 2013.
© 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society
intact. She did not have any respiratory symptoms, including pharyngitis. No crackles were detected in the lungs bilaterally. Chest X-ray showed no consolidation. The throat-swab rapid strep test was negative for GAS antigens. Laboratory tests showed an elevated white blood cell count of 34 100/mL (89.0% segmented neutrophils), with a hemoglobin level of 12.1 g/dL and a platelet count of 301 000/mL. Blood urea nitrogen was 24.3 mg/dL, uric acid 7.2 mg/dL, and creatinine (Cr) 0.50 mg/ dL. Serum albumin and total cholesterol were 4.0 g/dL and 141 mg/dL, respectively. Urinalysis indicated 50–99 white blood cells, and >100 red blood cells per high-power field, negativity for nitrite, and a protein level of 3+ . The spot urine protein/creatinine ratio was 0.89. Serum C3 was 10.9 mg/dL (normal range, 80–160 mg/dL), C4 25.0 mg/dL (normal range, 10–40 mg/dL), and CH50 ⱕ12.0 U/mL (normal range, 25.0– 48.0 U/mL). Serum anti-streptolysin O (ASO) was elevated to 1040 IU/mL. Blood and sputum culture indicated the presence of penicillin-intermediate S. pneumoniae 6C, although urine and throat cultures were negative. The patient was not vaccinated against pneumococcus. Renal ultrasonography showed normal sized kidneys bilaterally, with a slightly increased echogenicity. The patient was managed by treatment with i.v. cefotaxime and maintenance of hydration. The fever immediately disappeared, but on the third day, she became oliguric and her Cr level increased to a high of 0.66 mg/dL. The patient underwent successful diuresis over the next 4 days and the edema rapidly improved. Macrohematuria and proteinuria gradually disappeared by the seventh and ninth days, respectively. At discharge, Cr was 0.35 mg/dL, and only microhematuria persisted. At
PSAGN associated with pneumococcal infection 1 month follow up, C3 and CH50 had returned to normal and the ASO titer had decreased to 672 IU/mL. Microhematuria persisted for 8 months and then resolved.
Discussion We report here a pediatric patient with PSAGN associated with pneumococcal bacteremia. Although it is difficult to clarify the actual etiology, the present clinical findings can be explained by three possibilities. First, the patient had pneumococcal AGN and the ASO titer was elevated regardless of streptococcal infection. Second, the patient had PSAGN and pneumococcal infection independently. Third, the patient had PSAGN, which became more severe due to pneumococcal infection. Elevated ASO titer significantly indicates the existence of streptococcal infection. Nephritis was simultaneous with fever due to pneumococcal infection, indicating that the present patient had pneumococcal infection after the development of PSAGN, because the latent period should be sufficient between infection and onset of AGN to form immune complexes. Hence, the PSAGN might be discovered only at the time of pneumococcal infection, in the form of pneumococcal bacteremia, indicating that PSAGN without macrohematuria or heavy proteinuria may go unrecognized. Taken together, the third possibility is most likely in the present case. Acute glomerulonephritis associated with pneumococcal infection has certain specific characteristics, as previously reported: the interval between the primary pneumococcal infection and AGN is approximately 24–48 h; reversible hypocomplementemia occurs, as shown by laboratory tests; and renal failure is commonly mild, transient and reversible, although a few patients have required a short period of dialysis.1–7 Although the present clinical course was consistent with previous reports on pneumococcal AGN, it is improbable that pneumococcal infection was responsible for the increase in ASO titers. Further, the signs and symptoms of AGN, which could have been induced by immune complexes, appeared within a few days in the present patient. There are only four reported cases of S. pneumoniae being isolated from the blood in pediatric AGN (Table 1).1–4 All four
e137
cases involved serious infection such as pneumonia, bacteremia and/or meningitis. Interestingly, high ASO titers were also observed in two of the patients.1,4 With regard to the pathogenesis of hypocomplementemia in previous reports, it is suggested that pneumococcal AGN results from the deposition of immune complexes or antigens in the glomeruli, with the activation of classical and/or alternative complement pathways.1,2,5 The time interval between streptococcal infection and the first symptom of AGN is usually around 9–16 days for respiratory or skin infections,8 and within 3 days for pneumococcal infection.1–4 A few days might be relatively too short a period for the formation of immune complexes and renal compromise with any microbial agent. Although a detailed mechanism for the high ASO titer and short interval was not provided in previous reports of pneumococcal AGN,1,4,7 all the case reports, including the present one, support the hypothesis that invasive pneumococcal infection itself could be responsible for the complement reaction leading to PASGN. It is reported that high ASO titer and transient hypocomplementemia were observed in cases of febrile AGN associated with pneumonia caused by Mycoplasma pneumoniae or unidentified bacteria.4,9,10 These findings imply that PSAGN might be seen in association with not only pneumococcal, but also other microbial infections. The present report has some limitations. First, we did not perform renal biopsy. Although biopsy may have been diagnostically helpful, it is not generally performed in cases of PSAGN or pneumococcal AGN due to the rapid clinical improvement. In the present case, after discharge, proteinuria and microhematuria disappeared and the patient did not relapse into nephritis. This implies that nephritis due to IgA nephropathy or chronic kidney diseases was unlikely in the present patient. Second, the pneumococcus type 6C detected in the present patient has not been reported as a nephritogenic strain, although pneumococcal serotypes 5, 7, 9, 14, 15, and 17F have been suggested to be nephritogenic.1–6 The nephritogenic potential of pneumococcus type 6 therefore, requires further investigation. In conclusion, it is important to consider PSAGN associated with a microbial infection such as S. pneumoniae, when faced with a febrile patient with AGN.
Table 1 Characteristics of AGN associated with S. pneumoniae isolated from blood Reference
Age Gender Pneumonia Interval between Type of ASO (years) fever and organism nephritis (days) Present case 4 F – 1 6C (PISP) High (1040 IU/mL) 4 M + 3 17F (PSSP) High (400.9 Lechon et al. Todd units) 20104 Phillips et al. 6 F +
Pediatrics International (2013) 55, e136–e138
doi: 10.1111/ped.12150
Patient Report
Post-streptococcal acute glomerulonephritis associated with pneumococcal infection Satoshi Hibino,1 Akihiro Hoshino,1 Takanari Fujii,1 Yoshifusa Abe,1 Shuichiro Watanabe,2 Osamu Uemura3 and Kazuo Itabashi1 1 Department of Pediatrics, Showa University School of Medicine, 2Watanabe Children’s Clinic, Tokyo and 3Department of Pediatric Nephrology, Aichi Children’s Health and Medical Center, Aichi, Japan Abstract
Streptococcus pyogenes is the most common cause of post-infectious glomerulonephritis. Described herein is the case of a 5-year-old girl with febrile post-streptococcal acute glomerulonephritis (PSAGN) associated with pneumococcal bacteremia. The chief complaints were fever and macrohematuria without respiratory symptoms. Urinalysis indicated a protein level of 3+. Serological data showed elevated anti-streptolysin O (ASO) and hypocomplementemia. Blood culture was positive for S. pneumoniae. Her acute renal failure was mild and improved over several days. Although PSAGN was confirmed by elevated ASO and transient hypocomplementemia, the clinical course was consistent with those of several reported cases of AGN associated with pneumococcal infection. To our knowledge, there have been few reports on the relationship between pneumococcal infection and the incidence of PSAGN. We suggest the hypothesis that pneumococcal infection itself could exaggerate the complement reaction leading to PSAGN. It is important to consider PSAGN associated with a microbial infection such as S. pneumoniae when faced with a febrile patient with AGN.
Key words pneumococcal infection, post-streptococcal acute glomerulonephritis.
Group A b-hemolytic Streptococcus (GAS), specifically Streptococcus pyogenes, is the most common cause of post-infectious glomerulonephritis. Although other infectious causes are less common, several cases of acute glomerulonephritis (AGN) following infection with S. pneumoniae have been reported.1–7 We report here a pediatric patient with febrile post-streptococcal acute glomerulonephritis (PSAGN) associated with pneumococcal bacteremia. Interestingly, the present clinical course was consistent with those of prior reported cases of AGN associated with pneumococcal infection.1–7 To our knowledge, there have been few reports on the relationship between pneumococcal infection and the incidence of PSAGN. We suggest the hypothesis that pneumococcal infection itself could exaggerate the complement reaction leading to PSAGN.
Case report A 5-year-old Japanese girl was referred to hospital for gross hematuria and fever for 2 days. The findings of physical examination were as follows: body temperature, 39.3°C; pulse rate, 157 beats/min; respiratory rate, 22 breaths/min; and blood pressure, 100/53 mmHg. She had slight palpebral edema and edema of her face and legs bilaterally. The tympanic membrane was
Correspondence: Yoshifusa Abe, MD, PhD, Department of Pediatrics, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawaku, Tokyo 142-8666, Japan. Email: [email protected] Received 19 December 2012; revised 23 April 2013; accepted 31 May 2013.
© 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society
intact. She did not have any respiratory symptoms, including pharyngitis. No crackles were detected in the lungs bilaterally. Chest X-ray showed no consolidation. The throat-swab rapid strep test was negative for GAS antigens. Laboratory tests showed an elevated white blood cell count of 34 100/mL (89.0% segmented neutrophils), with a hemoglobin level of 12.1 g/dL and a platelet count of 301 000/mL. Blood urea nitrogen was 24.3 mg/dL, uric acid 7.2 mg/dL, and creatinine (Cr) 0.50 mg/ dL. Serum albumin and total cholesterol were 4.0 g/dL and 141 mg/dL, respectively. Urinalysis indicated 50–99 white blood cells, and >100 red blood cells per high-power field, negativity for nitrite, and a protein level of 3+ . The spot urine protein/creatinine ratio was 0.89. Serum C3 was 10.9 mg/dL (normal range, 80–160 mg/dL), C4 25.0 mg/dL (normal range, 10–40 mg/dL), and CH50 ⱕ12.0 U/mL (normal range, 25.0– 48.0 U/mL). Serum anti-streptolysin O (ASO) was elevated to 1040 IU/mL. Blood and sputum culture indicated the presence of penicillin-intermediate S. pneumoniae 6C, although urine and throat cultures were negative. The patient was not vaccinated against pneumococcus. Renal ultrasonography showed normal sized kidneys bilaterally, with a slightly increased echogenicity. The patient was managed by treatment with i.v. cefotaxime and maintenance of hydration. The fever immediately disappeared, but on the third day, she became oliguric and her Cr level increased to a high of 0.66 mg/dL. The patient underwent successful diuresis over the next 4 days and the edema rapidly improved. Macrohematuria and proteinuria gradually disappeared by the seventh and ninth days, respectively. At discharge, Cr was 0.35 mg/dL, and only microhematuria persisted. At
PSAGN associated with pneumococcal infection 1 month follow up, C3 and CH50 had returned to normal and the ASO titer had decreased to 672 IU/mL. Microhematuria persisted for 8 months and then resolved.
Discussion We report here a pediatric patient with PSAGN associated with pneumococcal bacteremia. Although it is difficult to clarify the actual etiology, the present clinical findings can be explained by three possibilities. First, the patient had pneumococcal AGN and the ASO titer was elevated regardless of streptococcal infection. Second, the patient had PSAGN and pneumococcal infection independently. Third, the patient had PSAGN, which became more severe due to pneumococcal infection. Elevated ASO titer significantly indicates the existence of streptococcal infection. Nephritis was simultaneous with fever due to pneumococcal infection, indicating that the present patient had pneumococcal infection after the development of PSAGN, because the latent period should be sufficient between infection and onset of AGN to form immune complexes. Hence, the PSAGN might be discovered only at the time of pneumococcal infection, in the form of pneumococcal bacteremia, indicating that PSAGN without macrohematuria or heavy proteinuria may go unrecognized. Taken together, the third possibility is most likely in the present case. Acute glomerulonephritis associated with pneumococcal infection has certain specific characteristics, as previously reported: the interval between the primary pneumococcal infection and AGN is approximately 24–48 h; reversible hypocomplementemia occurs, as shown by laboratory tests; and renal failure is commonly mild, transient and reversible, although a few patients have required a short period of dialysis.1–7 Although the present clinical course was consistent with previous reports on pneumococcal AGN, it is improbable that pneumococcal infection was responsible for the increase in ASO titers. Further, the signs and symptoms of AGN, which could have been induced by immune complexes, appeared within a few days in the present patient. There are only four reported cases of S. pneumoniae being isolated from the blood in pediatric AGN (Table 1).1–4 All four
e137
cases involved serious infection such as pneumonia, bacteremia and/or meningitis. Interestingly, high ASO titers were also observed in two of the patients.1,4 With regard to the pathogenesis of hypocomplementemia in previous reports, it is suggested that pneumococcal AGN results from the deposition of immune complexes or antigens in the glomeruli, with the activation of classical and/or alternative complement pathways.1,2,5 The time interval between streptococcal infection and the first symptom of AGN is usually around 9–16 days for respiratory or skin infections,8 and within 3 days for pneumococcal infection.1–4 A few days might be relatively too short a period for the formation of immune complexes and renal compromise with any microbial agent. Although a detailed mechanism for the high ASO titer and short interval was not provided in previous reports of pneumococcal AGN,1,4,7 all the case reports, including the present one, support the hypothesis that invasive pneumococcal infection itself could be responsible for the complement reaction leading to PASGN. It is reported that high ASO titer and transient hypocomplementemia were observed in cases of febrile AGN associated with pneumonia caused by Mycoplasma pneumoniae or unidentified bacteria.4,9,10 These findings imply that PSAGN might be seen in association with not only pneumococcal, but also other microbial infections. The present report has some limitations. First, we did not perform renal biopsy. Although biopsy may have been diagnostically helpful, it is not generally performed in cases of PSAGN or pneumococcal AGN due to the rapid clinical improvement. In the present case, after discharge, proteinuria and microhematuria disappeared and the patient did not relapse into nephritis. This implies that nephritis due to IgA nephropathy or chronic kidney diseases was unlikely in the present patient. Second, the pneumococcus type 6C detected in the present patient has not been reported as a nephritogenic strain, although pneumococcal serotypes 5, 7, 9, 14, 15, and 17F have been suggested to be nephritogenic.1–6 The nephritogenic potential of pneumococcus type 6 therefore, requires further investigation. In conclusion, it is important to consider PSAGN associated with a microbial infection such as S. pneumoniae, when faced with a febrile patient with AGN.
Table 1 Characteristics of AGN associated with S. pneumoniae isolated from blood Reference
Age Gender Pneumonia Interval between Type of ASO (years) fever and organism nephritis (days) Present case 4 F – 1 6C (PISP) High (1040 IU/mL) 4 M + 3 17F (PSSP) High (400.9 Lechon et al. Todd units) 20104 Phillips et al. 6 F +
