|Year : 2013 | Volume
| Issue : 4 | Page : 264-269
A review of postinfectious glomerulonephritis cases from a tertiary care renal referral center in South India
Sujatha Siddappa1, R Kowsalya2, KM Mythri3
1 Department of Pathology, Institute of Nephrourology, Victoria Hospital Campus, Bangalore, Karnataka, India
2 Department of Biochemistry, Institute of Nephrourology, Victoria Hospital Campus, Bangalore, Karnataka, India
3 Department of Microbiology, Institute of Nephrourology, Victoria Hospital Campus, Bangalore, Karnataka, India
|Date of Web Publication||7-Feb-2014|
Department of Pathology, Institute of Nephrourology, Victoria Hospital Campus, Bangalore - 560 002, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Postinfectious glomerulonephritis is an immune mediated renal disease and one of the causes for end stage renal disease in developing countries like India. The disease spectrum has changed significantly in the past few decades. The goal of this study is to review the prevalence and clinicopathological spectrum of the disease in a major tertiary care renal referral hospital. Materials and Methods: Between July 2007 and July 2012, 54 cases of postinfectious glomerulonephritis were identified at our medical center. The patients' records were retrospectively reviewed with respect to clinical presentation, laboratory, histopathology, and clinical course. Results: There were 32 males and 22 females. The mean age was 24.1 years. Twenty six percent of patients presented with acute renal failure and required dialysis support during the course of disease. Hypocomplementemia was present in about 90% of the patients. Histologically, characteristics showed distinct patterns of glomerulonephritis with predominant "starry sky pattern" on immunofluorescence. At the last follow-up, none of the patients were dialysis-dependent, and 53% were in complete remission. Conclusions: We hereby report cases of postinfectious glomerulonephritis with history of recurrence and cross infection to highlight the importance of treatment and awareness regarding this preventable cause of chronic renal disease.
Keywords: Dialysis, glomerulonephritis, postinfectious, prevalence, renal disease
|How to cite this article:|
Siddappa S, Kowsalya R, Mythri K M. A review of postinfectious glomerulonephritis cases from a tertiary care renal referral center in South India. Int J Health Allied Sci 2013;2:264-9
|How to cite this URL:|
Siddappa S, Kowsalya R, Mythri K M. A review of postinfectious glomerulonephritis cases from a tertiary care renal referral center in South India. Int J Health Allied Sci [serial online] 2013 [cited 2020 Feb 23];2:264-9. Available from: http://www.ijhas.in/text.asp?2013/2/4/264/126745
| Introduction|| |
Postinfectious glomerulonephritis (PIGN) is one of the oldest recognized renal diseases worldwide. It is considered a benign transient condition, but long-term follow-up has shown that it might progress to end stage renal disease (ESRD).  It typically develops 1-3 weeks after an episode of acute bacterial infection commonly by group A beta hemolytic streoptococci. But over the years, the organisms have become increasingly diversified with Staphylococcus and other gram negative organisms also emerging as major causative agent.  Added to this there are patients with double glomerulopathy, with either coexistence of two different glomerulopathies of which one is PIGN or superimposition of a second glomerulopathy onto first already underlying renal disease. Postinfectious glomerulonephritis may occur as superimposed glomerulopathy with chronic glomerulonephropathies such as minimal change nephrotic syndrome, membranous glomerulonephritis, immunoglobulin (Ig). A nephropathy and thin basement membrane nephropathy. 
Though the incidence of postinfectious glomerulonephritis has lowered in past few decades, reports of epidemics and clusters of cases continue to appear worldwide. It is usually seen in children and accounts for about 21% of children admitted to hospital with acute renal failure in developing countries.  A review estimated that over 470,000 cases of acute poststreptococcal glomerulonephritis occur annually worldwide and 97% of these cases were in less developed countries.  These numbers represent only the clinically diagnosed cases and when household contacts and family members are screened the overt and subclinical cases of nephritis has been found to be four to 19 times higher. Approximately, 5,000 deaths annually have also been reported in the reviews. ,
In India, postinfectious glomerulonephritis is still the commonest cause for hospital admission in children and about 13-27% of cases of renal failure are due to postinfectious glomerulonephritis of streptococci origin.  But there is paucity of data in adults as infective glomerulonephritis is probably an overlooked cause of ESRD. Hence, the aim of this study was to highlight the prevalence and clinicopathological profile of postinfectious glomerulonephritis in a major tertiary care renal referral hospital.
| Materials and Methods|| |
All cases of native renal biopsies performed from July 2007 to July 2012 in our institute were reviewed retrospectively in the study. A total of 884 native biopsies were performed during this period among these biopsies, 54 cases were diagnosed as postinfectious glomerulonephritis.
Clinical and laboratory assessment
The patients were reviewed with respect to the clinical data including age, sex, skin or throat infection, blood pressure, systemic manifestations of renal failure, and history of medications. The laboratory parameters included urinalysis, serum creatinine, blood urea, complete blood counts, plasma protein, albumin, cholesterol, 24-h urinary protein excretion, antistreptolysin-O (ASO) titer, and complement levels.
Renal biopsy was processed routinely for light and immunofluorescence (IF) microscopy.
Patients were treated according to their clinical and renal symptoms. Patients with mild renal dysfunction were treated with antibiotics and supportive therapy. While patients with rapidly deteriorating renal function received steroids, that is, intravenous methylprednisolone in a dose of 10 mg/kg/day for 5 days followed by oral prednisolone in a dose of 1 mg/kg/day for 4 weeks and tapered thereafter. Additionally mycophenolate mofetil (1-3 g/day) pulse was added with steroids to patients with crescents on biopsy.
| Results|| |
The study comprised of 32 males and 22 females with the mean age of 24.1 ± 12.35 years at the time of presentation.
Ten patients were aged between 8 and 16 years and the peak age of disease occurrence was observed in 2 nd decade of life.
All the cases were sporadic and generally the patients were from a low socioeconomic background. The disease was preceded by acute streptococcal infection in 18 patients, while four patients had complaints of skin infection before admission. But there was no active focus of skin or upper respiratory infection at the time of presentation. None of the patients had any predisposing factors such as diabetes or immunosuppression.
The mean duration of symptoms before the diagnosis of nephritis was 3 months (ranging from 7 days to 12 months). Fever was the main presenting complaint followed by edema and urinary abnormalities. Of the triad of features, edema was seen in 85% of patients, hematuria in 40% of patients, and fever in all the patients. At presentation six patients had hypertension and were on treatment, while three patients had new onset hypertension. Six patients including a child (10-year-old) presented with acute renal failure requiring admission to intensive care unit requiring dialysis support. [Table 1] shows the demographics and presenting symptoms.
Clustering of cases
While two patients had a past history of disease recurrence and another two cases had similar disease affliction in a family member. One of the cases was of twin brothers aged 10 years referred to our institution for further evaluation of hematuria and management of renal impairment. The elder twin had similar complaints about a year back and had been adequately treated and the second twin warranted a biopsy due to persistence of proteinuria. Another case was of a 45-year-old female with intermittent fever associated with swelling of lower limbs and decreased urine output. Her husband also had similar complaints 6 months back and had been treated.
Methicillin resistant Staphylococcus aureus (MRSA) associated postinfectious glomerulonephritis
A 23-year-old female presented with peuperal sepsis with deterioration of renal function. On investigation a high vaginal swab showed presence of MRSA and on biopsy showed features of postinfectious glomerulonephritis with a negative IF study.
There were 12 cases of postinfectious glomerulonephritis superimposed on nephrotic glomerulopathy, probably minimal change disease. These cases presented with persistence of nephrotic range proteinuria and on biopsy showed features of postinfectious glomerulonephritis with a negative IF study. Three cases with persistent nephrotic range proteinuria have been followed-up and rebiopsied after 12 months showing resolution of the acute phase with minimal change disease.
Postvaccination postinfectious glomerulonephritis
A 10-year-old boy presented with features of nephrotic syndrome 1 week post vaccination. On renal biopsy, mesangial expansion with mild increase of cellularity was seen. There was polymorphonuclear infiltration of the glomeruli with mild acute tubular necrosis, presence of red blood cell (RBC) casts, and protein casts consistent with features of postinfectious glomerulonephritis with a negative IF study.
The laboratory results showed presence of anemia in all the patients with mean hemoglobin of 8.9 g/dl and a raised erythrocyte sedimentation rate above 60 mm/h. Seventy percent (38 patients) showed mild to moderate leukocytosis. The mean serum creatinine was 2.98 mg/dl with 18 patients having normal range of creatinine. Proteinuria was present in all the patients, with 60% having nephrotic range proteinuria. Urine microscopy showed pyuria and bacteremia in about 70% of the patients. [Table 2] shows the mean values of the laboratory data.
Throat swab cultures revealed normal bacterial flora except in 10 patients which showed growth of Staphylococcus and Streptococci in two patients. Urine culture yielded insignificant bacteruria in 15 cases and growth of gram negative organisms Escherichia More Details coli in 12 patients, and no growth in the remaining patients. Elevated ASO titers were seen in 24 patients and negative in all others. Low C3 levels were found in 90% of patients with normal/slightly low C4 levels.
On light microscopy, all the biopsies showed features of endocapillary proliferation focal segmental, mesenglial hypercellurality with matrix expansion and neutrophilic exudation and absence of crescents. Interstitium was edematous with diffuse mild to moderate mixed inflammation. Cells comprised of neutrophils, lymphocytes, and eosinophils. Tubules showed RBC casts, with mild degree of acute tubular necrosis. Blood vessels were generally unremarkable except in cases with hypertension showed medial hyperplasia. [Figure 1] shows glomeruli with lobulated appearance with polymorphonuclear cell infiltrate.
|Figure 1: Glomeruli showing lobulated appearance with polymorphonuclear cell infiltrate|
Click here to view
On IF coarse peripheral granular deposits of complement C3 was seen in all the cases. The most common staining pattern on IF was granular mesangial and glomerular capillary wall, resembling the "starry sky pattern" described by Sorger et al.  [Figure 2] shows the starry sky appearance on IF.
There were two cases of postinfectious crescentric glomerulonephritis which presented with oliguria and showed predominant cellular infiltration with cellular crescents on biopsy.
All the patients with known infection were treated with antibiotics. Seven patients were treated with steroids for 4 weeks of time. At the end of mean duration of follow-up of 24.2 ± 14.4 months; none of the patients were dialysis-dependent, three had developed hypertension, 25 patients (47%) had persistent renal dysfunction (as evidenced by serum creatinine >1.5 mg/dl), and 29 patients (53%) were in complete recovery. Four of the patients with persistent renal dysfunction were rebiopsied at the end of 12 months, which revealed minimal change with noncontributory IF finding in three cases, while one case was of focal segmental glomerulosclerosis.
| Discussion|| |
In the present study we have attempted to address the issue of postinfectious glomerulonephritis in patients with renal disorder attending a tertiary care referral center catering exclusively to renal and urology patients. This study demonstrates that postinfectious glomerulonephritis is a common cause of renal dysfunction with a prevalence of 6.2% in our hospital. Our study shows a closer prevalence to that reported by Das et al., with a prevalence of 8.1% in a series of biopsy proven renal diseases from south India.  Similar studies from other parts have reported a higher prevalence in 2 nd decade of life in men.  A similar pattern was observed in our study with mean age of 24.1 years and a higher disease rate in men.
Normally sporadic cases and epidemic outbreaks have been reported in communities with densely populated dwellings that have poor hygienic conditions with a high incidence of malnutrition, anemia, and intestinal parasites. All our cases were also sporadic and from a low socioeconomic backdrop. Tasic and Polenakovic, have reported the occurrence of subclinical nephritis in household contacts.  In our study too there were two cases with disease affliction in a family member. This may be due to inadequate treatment of the index cases, leading to increased risk of cross infection and disease recurrence. ,
The pathognomonic feature of postinfectious glomerulonephritis is the deposition of immune complexes in the glomerular basement membrane. The most widely proposed mechanism is deposition of immune mediated complexes by streptococcal proteins having unique antigenic determinants with particular affinity for sites within the normal glomerulus. Once bound to the glomerulus, they activate complement directly by interaction with properdin and attract inflammatory cells which actively synthesize proinflammatory cytokines in situ resulting glomerular inflammation. , The association of MRSA infection associated glomerulonephritis is on rise and should be differentiated from the other forms of primary nephropathy to avoid erroneous treatment with immunosuppressive therapy. 
Normally the patients are asymptomatic or may present with sudden appearance of hematuria, proteinuria, edema, hypertension, or dysuria along with low levels of complement. Because a high percentage of persons affected have mild disease and are asymptomatic, the actual incidence of the disease is not known.  In our study, all our patients had at least one episode of hematuria (micro/macroscopic) with variable amount of proteinuria. Nephrotic syndrome was the main mode of clinical presentation, followed by renal failure in accordance with most of the studies. This high occurrence of renal failure has been attributed lack of awareness of regarding the complications associated with infection and occurrence of superimposed glomerulopathy.
Postinfectious glomerulonephritis can occur as superimposed glomerulopathy with chronic glomerulonephropathies. We had 12 such cases superimposed on nephrotic glomerulopathy probably minimal change disease. These double glomerulonephritis are not rare and are found incidental findings on biopsy. They present with atypical clinical course and in most cases resolve completely. 
The clinical course is largely predictable. In most cases, hypertension subsides, renal function returns to normal and all urinary abnormalities eventually disappear.  Persistent hematuria and proteinuria for more than 12 months suggest possibility that the disease has entered a chronic phase. Although renal biopsy is rarely indicated, it has contributed substantially to the understanding of disease process. A direct correlation exists between the severity of histologic process and clinical manifestation of the disease and possibly prognosis. The typical histopathology is one of diffuse cellular proliferation in the glomerulus with an exudate containing neutrophils and monocytes and variable degrees of complement and immunoglobulin deposition. Presence of crescents indicates a severe form of glomerulonephritis that usually progresses rapidly to renal failure. The persistence of hypertension and nephrotic range proteinuria during the follow-up are major bad prognostic predictors for renal dysfunction. Hence, renal biopsy is considered in all patients with acute renal failure when renal function does not improve with antibiotic treatment as patients with presence of crescents on renal biopsy usually require treatment with steroids. ,,
Treatment remains largely supportive with appropriate antibiotics. The immediate prognosis is excellent, but acute disease can lead to severe acute renal failure requiring dialysis/or admission to intensive care. Hence, prompt and adequate treatment of the cases is necessary. Prophylactic use of antibiotics among family members has also been recommended to reduce the incidence of disease recurrence. 
In general, children are believed to have an excellent prognosis with the majority showing complete recovery; but adults have a poorer prognosis with overall only 60% recovering completely.  The rest develop hypertension or renal impairment and approximately 25% progress to chronic renal failure.  In our study we found a similar finding with 53% patients recovering completely. Adults with comorbidities such as diabetes and alcoholism are found to be at increased risk for developing chronic renal failure. Hence, all patients with acute postinfectious glomerulonephritis should be treated as though they have active infection. Regular follow-up and monitoring of blood pressure, renal function test, and urine for hematuria and proteinuria every 3-6 months after the acute phase for at least a year is recommended to prevent progression to chronic renal failure. 
Prevention of epidemics of postinfectious glomerulonephritis requires an active community participation in controlling the infection. , Improvement in housing, especially reduction in overcrowding, will hinder spread of infectious disease. Awareness of infection risk and prevention strategies at grass root level is essential to lessen the burden of renal diseases in our country. So in developing countries like India with limited resources and a burden of 150-200 per million population (pmp) ESRD, a heightened awareness and appropriate management of postinfectious glomerulonephritis patients is imperative for a better outcome and prevention of renal diseases. 
| Conclusion|| |
Postinfectious glomerulonephritis is still an endemic infectious condition in India and other parts of world. Hence, awareness in prevention and treatment of postinfectious glomerulonephritis may contribute to reducing the incidence of renal disease and renal failure in future.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]