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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2018  |  Volume : 29  |  Issue : 3  |  Page : 623-629
Crescentic infection related glomerulonephritis in adult and its outcome


Institute of Nephrology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India

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Date of Submission24-Apr-2017
Date of Decision23-Jun-2017
Date of Acceptance25-Jun-2017
Date of Web Publication28-Jun-2018
 

   Abstract 

The epidemiology of infection-related glomerulonephritis (IRGN) is changing in recent times both in developed and developing nations. Although published studies showed renal outcome in adult IRGN was not as benign as in children, literature regarding clinical profile and outcome of crescentic form of adult IRGN is scarce; hence, we aimed to study the clinical profile of crescentic IRGN. We conducted a retrospective observational study in patients with crescentic IRGN in adults at the Department of Nephrology, Madras medical college, Chennai between 2009 and 2014. A total of 47 patients were included with a mean follow-up of 9.9 ± 4.2 months. The mean age was 42 ± 13.5 years. About 19.1% of patients had diabetes. The skin was the most common site of infection (38.3%) with methicillin-resistant Staphylococcus acareas (MRSA) as the most common organism. Hypocomplementemia was present in 100% in our study. Hemodialysis (HD) was required in 53.2% of patients and oral steroids were given in 78.7%. Complete renal recovery was seen only in 25.5%, progression to chronic kidney disease in 40.4%, seven patients reached end-stage renal disease, and nine patients died during follow-up. On univariate analysis, MRSA infection, the unidentified source of infection, nonisolation of organisms presence of interstitial fibrosis and tubular atrophy in renal biopsy and requirement of HD were found to be significant risk factors for poor renal outcome. In our study, crescentic form of IRGN is associated with poor renal outcome.

How to cite this article:
Sakthirajan R, Dhanapriya J, Nagarajan M, Dineshkumar T, Balasubramaniyan T, Gopalakrishnan N. Crescentic infection related glomerulonephritis in adult and its outcome. Saudi J Kidney Dis Transpl 2018;29:623-9

How to cite this URL:
Sakthirajan R, Dhanapriya J, Nagarajan M, Dineshkumar T, Balasubramaniyan T, Gopalakrishnan N. Crescentic infection related glomerulonephritis in adult and its outcome. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2022 May 25];29:623-9. Available from: https://www.sjkdt.org/text.asp?2018/29/3/623/235169

   Introduction Top


Infection-related glomerulonephritis (IRGN) is an immune-mediated glomerulonephritis caused by nonrenal bacterial infections[1] and incidence of IRGN in adults is estimated to 2 and 0.3 cases/100,000 person-years in developing and developed countries, respectively[2] In contrary to IRGN in children, adults usually present with skin as predominant source of infection (triggered by nonstreptococcal infections and Gram-negative organisms) and with signs of volume overload and congestive failure rather than seizures. The outcome of IRGN is also poor in adults with the risk of end-stage renal disease (ESRD) and chronic kidney disease (CKD) in the long term.[3],[4] Although the existing literature describes in detail, the natural history of IRGN with endocapillary proliferation, studies are not done in crescentic IRGN in adults. In this study, we analyzed the risk factors, etiology, clinical features, and outcome of crescentic IRGN.


   Materials and Methods Top


We did a retrospective observational study in patients with age >18 years and biopsy-proven crescentic form of IRGN during 2009–2014 in our center. Those patients with double contouring of glomerular basement membrane in silver methenamine stain, complement deposits alone without immunoglobulins and persistent serum hypocomplementemia after 12 weeks and positive for antinuclear antibody and anti-hepatitis C virus antibody were excluded from the study. Clinical data including antecedent infection, comorbid illness, presenting symptomatology and investigations such as urinalysis, urine spot protein-creatinine ratio, serum creatinine, complete blood count, serum antistreptolysin O (ASO) titer, complement (C3, C4), microbiological cultures were analyzed. The renal biopsy specimen was analyzed using light microscopy (LM) with hematoxylin and eosin and periodic acid–Schiff stains and immunofluorescence (IF).

Definition of the terms used as follows:

  1. Nephrotic proteinuria: urine spot protein creatinine ratio >3.5
  2. Hypertension: systolic blood pressure >140 mm Hg, diastolic blood pressure >90 mm Hg
  3. Crescentic GN: Crescents in more than 50% of the glomeruli in LM
  4. Staging of interstitial fibrosis and tubular atrophy (IFTA): mild 0-25%; moderate 25%-50%; severe >50% in LM
  5. Full-house IF: presence of 2+ or more of IgG, IgM, IgA, C3, and C1q
  6. Recovery: eGFR >60mL/min/1.73 m2 at three months
  7. CKD: eGFR <60 mL/min/1.73 m2 at three months
  8. ESRD: Dialysis dependent for <3 months.


Statistical analysis was performed by the statistical software STATA 11.0. Continuous variables are represented as “Mean (standard deviation),” and categorical variables are represented as “Frequency (percentage).” Chi-squared test or Fisher's exact tests were used to assess differences in categorical data. The value of P <0.05 was considered as statistically significant.


   Results Top


During the study period, we did 1715 renal biopsies of which 194 cases of IRGN were documented. Among IRGN cases, 47 patients (24.2%) had more than 50% crescents. Baseline characteristics, clinical and laboratory data of 47 patients are shown in [Table 1]. The mean age of the patients was 42 ± 13.5 years and was followed up for a mean period of 9.9 ± 4.2 months. The incidence of IRGN was common in the winter season (53.2%). Of them, 36.2% (n = 17) patients had comorbid illness with diabetes being the most common in 19.1% (n = 9), followed by rheumatic valvular disease in five patients, an alcohol-related chronic liver disease in two and one with HIV infection. The source of infection could be identified only in 66%, the skin was the most common (38.3%, n = 18), followed by urinary tract infection, diarrhea, and pneumonia [Figure 1]. The bacteriological cultures were positive only in 53.2% (n = 25), of which methicillin-resistant Staphylococcus aureus (MRSA) was the most common organism (23.4%, n = 11) as shown in [Figure 2]. Low C3 was seen in all patients and low C4 in four patients.
Table 1: Patient characteristics, clinical and laboratory data of patients.

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Figure 1: Source of infection.

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Figure 2: Bacteriological profile of study subjects.

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Elevated ASO (>200 U/L) was found in 59.6% (28 patients). Of them, 20 cases (skin - 15, bone - 1, pneumonia - 3, and otitis media) had active infection. Although ASO titers were elevated in 15 patients with skin infection, none had an active throat infection, and strep-toccoccus was isolated in three patients with pneumonia. All the patients with rheumatic heart disease were on oral penicillin prophylaxis, none had streptococcal infection, two had had MRSA, one Escherichia coli and in two no organisms were isolated.

In renal biopsy, all had crescents in >50% of glomeruli [Figure 3] and IFTA was present in 38.3% of specimens, of which 8.5% had mild IFTA, moderate in 23.4%, and severe in 6.3% of biopsies. In IF, C3c along with IgG was the most common deposit (70.2%, n = 33) and co-dominant deposits of IgA was present in seven. Interstitial infiltrates were patchy in 4% and diffuse in 26% of biopsies.
Figure 3: Renal biopsy showing cellular crescents (H and E).

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Hemodialysis was required in 53.2% (n = 25) of patients and pulse steroids in the form of methyl prednisolone 1 g intravenously for three days followed by oral steroids for eight to 12 weeks was given in 37 (78.7%) of patients. Steroids was not given in 10 patients (five had active infection, one had diarrhea and four patients were not willing for steroids). Regarding the outcome, complete recovery was documented only in 25.5% of cases, progression to CKD was found in 40.4%, seven patients reached ESRD and nine patients died (two due to cardiovascular disease during followup, one recovered and other had CKD and remaining 6 died due to sepsis including four patients who received steroids).

On statistical analysis, MRSA infection, unidentified source of infection, nonisolation of organisms, presence of IFTA in renal biopsy and requirement of dialysis were found to be significant risk factors for poor renal outcome [Table 2].
Table 2: Predictors for poor renal outcome.

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   Discussion Top


In contrast to childhood, epidemic poststreptococcal glomerulonephritis, which usually resolves spontaneously, sporadic adult IRGN has a guarded prognosis, with a significant proportion developing CKD or ESRD.[3],[4]The mean age of our study group was relatively younger (42 years) with a male predominance than the studies done by Nasr et al[5] and Wen al.[6] The incidence of IRGN has a seasonal preponderance with the highest in the winter season as witnessed in our previous study.[4] However, we could not find the exact link, as the skin infections are more common in the summer. Similar to Nasr et al[5] and Moroni et al,[3] the comorbid illness were found in 36.2% of our subjects with diabetes being most common. However, in contrast, rheumatic valvular heart disease was seen in 10.6% of our patients.

Streptococcus was the most frequent pathogen in children and developing countries, but in the antibiotic era, there was a change in the bacteriological profile and site of infection.[1] Similar to the studies done in the past decades.[1],[3],[5] The most common source of infection in our study was skin and MRSA being the most common organism. Further, in contrast to above studies, Montseny et al[7] and Moroni et al[3] had documented the presence of Gram-negative organisms in 14% and 22% of the cases, respectively. The study had Gram-negative organism in 21.2% of the cases, but the putative antigen related to pathophysiology remains in dark. Overall the active foci of infection were found only in 53.2% of patients and others presented generally with possible antecedent infection.

All the patients presented with signs of volume overload and renal failure, 87.2% had hypertension, 78.7% presented with RPGN and none had CNS manifestations. It is evident from other studies[5],[7] that crescentic form of IRGN could not be differentiated from diffuse proliferative form by the mere presence of renal failure or requirement of dialysis. The childhood crescentic form of IRGN[8] differs from the clinical features of adults (our study), in high incidence of macroscopic hematuria (87 vs. 8.5%) and low prevalence of hypo-complementemia (58.8 vs. 100%).The clinical manifestation in infection related crescentic GN differs from anti GBM disease and pauci immune crescentic GN by high prevalence of hypertension apart from hypocomplementemia.

In the renal biopsy, along with crescentic GN, IFTA was present in 38.3% of cases.C3 deposits were dominant in all with IgG being the most common immunoglobulin. Both Nasr et al and Moroni et al showed the presence of glomerular fibrinoid necrosis in 19% and 16% of biopsies, respectively, but in contrast, none of our biopsy specimen had necrosis. Similarly, interstitial infiltrates in our cases were less only in 31% compared to 36% in Moroni et al and 95% in Nasr et al. In the review by Jennette and Thomas[9] an analysis of 6000 native kidney biopsy in the UNC nephro-pathology laboratory among the PIGN biopsy samples, only 4% had crescentic form of IRGN. However in our center, 24.2% of IRGN samples had crescentic form which portends that the natural history of IRGN differs in different population and ethnicity. There was no statistical correlation between type of immunoglobulin deposits and renal outcome similar to other studies.[3],[4],[5] IgA deposits were found in seven patients of which only one had normal recovery of renal function, three reached ESRD, two patients died and one had CKD.

Renal replacement therapy was given in 53.2% of patients. Steroids were given in 78.7% of patients along with appropriate antibiotic therapy, but steroid therapy had no significant impact over the renal outcome. Both Nasr et al[5] and Moroni et al[3] considered steroids in the management of IRGN in patients presenting with either renal insufficiency or crescents, but did not find any influence on the outcome. Due to the paucity of literature in the role of steroids, even the KDIGO guidelines suggested RCT with corticosteroids in the treatment of crescentic form of IRGN.[10] However, our study results clearly showed that steroids alone will not be enough in the management of crescentic IRGN in improving the renal survival. Hence, along with antigenic clearance by antibiotics, whether simultaneous removal of circulating immune complexes by extracorporeal therapy and immunoglobulins will improve renal outcome needs additional research.

The complete renal recovery occurred only in 25.5% of cases, progression to CKD was found in 40.4%, seven patients reached ESRD and nine patients died due to infection during follow-up. Compared to the diffuse proliferative form of IRGN in adults the renal outcome of crescentic form is grave.[3],[4],[5] Further, studies done by Srivastava et al[11] and El-Husseini et al[8] in children with crescentic PIGN also portends poor prognosis. MRSA infection had significant negative correlation with renal outcome compared to other studies in adults.[1] Similar to Nasr et al, the presence of IFTA in renal biopsy and requirement of dialysis were found to be significant risk factors for poor renal outcome. Further, Moroni et al found presence of interstitial inflammation as one of the poor predictors of renal recovery. Age, presence of comorbid illness, serum creatinine at presentation, nephrotic range proteinuria, and steroid therapy had no influence on the renal outcome in our study.

Recently, Baikunje et al[12] published nine patients of PIGN with crescents in adults showed beneficial effect of steroids on renal outcomes, but mean percentage of glomeruli with crescents was only 36.13%. In a prospective study of primary glomerulonephritis in 137 patients, seven patients with were IRGN included out of which 28.6% presented as rapidly progressive glomerulonephritis.[13]

Limitation of our study include retrospective study and we were not able perform electron microscopy due to logistic reasons.

To conclude, there is an increasing incidence of crescentic form of IRGN which differs from the diffuse proliferative form by concurrent foci of infection which predominantly involves skin. The bacteriological profile also differs by MRSA being the most common organism and rising trend of Gram-negative bacteria as a casual association. The lack of literature evidence adds to the complexity in the management of crescentic IRGN leading to poor renal outcome.


   Acknowledgment Top


We would like to thank Dr. Anila Abraham Kurien MD, Renopath, Chennai for her help in evaluating renal biopsy specimens and S. Gothai Nachiyar for statistical analysis.

Conflict of interest: None declared.

 
   References Top

1.
Nasr SH, Radhakrishnan J, D'Agati VD. Bacterial infection-related glomerulonephritis in adults. Kidney Int 2013;83:792-803.  Back to cited text no. 1
    
2.
Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infect Dis 2005;5:685-94.  Back to cited text no. 2
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3.
Moroni G, Pozzi C, Quaglini S, et al. Longterm prognosis of diffuse proliferative glome-rulonephritis associated with infection in adults. Nephrol Dial Transplant 2002;17:1204-11.  Back to cited text no. 3
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4.
Natarajan G, Ramanathan S, Jeyachandran D, et al. Follow-up study of post-infectious glomerulonephritis in adults: Analysis of predictors of poor renal outcome. Saudi J Kidney Dis Transpl 2014;25:1210-6.  Back to cited text no. 4
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5.
Nasr SH, Fidler ME, Valeri AM, et al. Postinfectious glomerulonephritis in the elderly. J Am Soc Nephrol 2011;22:187-95.  Back to cited text no. 5
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6.
Wen YK. The spectrum of adult postinfectious glomerulonephritis in the new millennium. Ren Fail 2009;31:676-82.  Back to cited text no. 6
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7.
Montseny JJ, Meyrier A, Kleinknecht D, Callard P. The current spectrum of infectious glomerulonephritis. Experience with 76 patients and review of the literature. Medicine (Baltimore) 1995;74:63-73.  Back to cited text no. 7
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8.
El-Husseini AA, Sheashaa HA, Sabry AA, Moustafa FE, Sobh MA. Acute postinfectious crescentic glomerulonephritis: Clinicopathologic presentation and risk factors. Int Urol Nephrol 2005;37:603-9.  Back to cited text no. 8
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9.
Jennette JC, Thomas DB. Crescentic glomeru-lonephritis. Nephrol Dial Transplant 2001;16: 80-2.  Back to cited text no. 9
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10.
Kid International 2; 2012. Available from: http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO-GN-Guideline.  Back to cited text no. 10
    
11.
Srivastava RN, Moudgil A, Bagga A, et al. Crescentic glomerulonephritis in children: A review of 43 cases. Am J Nephrol 1992;12: 155-61.  Back to cited text no. 11
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12.
Baikunje S, Vankalakunti M, Nikith A, et al. Post-infectious glomerulonephritis with crescents in adults: A retrospective study. Clin Kidney J 2016;9:222-6.  Back to cited text no. 12
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13.
Modugumudi AS, Venkata PB, Bottla SK, et al. A study of primary glomerular diseases in adults; clinical, histopathological and immuno-fluorescence correlations. J Nephropharmacol 2016;5:91-7.  Back to cited text no. 13
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Correspondence Address:
Dr. Jeyachandran Dhanapriya
Institute of Nephrology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.235169

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