| Abstract|| |
Post-infectious glomerulonephritis (PIGN) still remains one of the most common glomerulonephritis in the developing world. We studied the epidemiology and clinical spectrum of PIGN in adults to identify the clinical, biochemical and histological factors that would predict renal outcome. Data of 102 adult PIGN patients treated between 2009 and 2011 with a mean follow-up of 12 months (6-36 months) were analyzed retrospectively. The mean age of the patients was 32.7 ± 15 years, with a male to female ratio of 1.2:1. At presentation, 99% of the patients had edema and oliguria, 73% had hypertension, 55% had macrohematuria and 60% had nephrotic range proteinuria. About 14% presented with complications (pulmonary edema-6%, seizure-1%, dialysis requiring renal failure-7%) and 9% had comorbid illness. Sixty percent of the patients had serum creatinine >2 mg/dL at presentation, which was persistent in 30% at the end of one week and 68% had hypo-complementemia. Renal biopsy revealed diffuse proliferative glomerulonephritis in 70% of the patients. At 12 months, 2% had persistent hypertension, 10% had persistent proteinuria and hematuria and 11% had serum creatinine >1.5 mg/dL. Univariate analysis with the Fischer Exact test revealed age >40 years, male gender, serum creatinine >2 mg/dL at one week, comorbid illness, requirement of dialysis, crescents in >30% glomeruli and persistent proteinuria and microscopic hematuria at 12 months as significant risk factors for poor renal outcome. Serum creatinine >2 mg/dL at one week and persistent proteinuria at 12 months were the independent risk factors that predicted poor renal outcome at one year.
|How to cite this article:|
Natarajan G, Ramanathan S, Jeyachandran D, Balasubramaniyan T, Srinivasa Prasad N D, Thanigachalam D. 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
|How to cite this URL:|
Natarajan G, Ramanathan S, Jeyachandran D, Balasubramaniyan T, Srinivasa Prasad N D, Thanigachalam D. Follow-up study of post-infectious glomerulonephritis in adults: Analysis of predictors of poor renal outcome. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2019 Nov 13];25:1210-6. Available from: http://www.sjkdt.org/text.asp?2014/25/6/1210/144254
| Introduction|| |
Post-infectious glomerulonephritis (PIGN) is an immune-mediated form of glomerulonephritis (GN) that commonly affects children after an upper respiratory or skin infection. , Recently, organisms other than streptococcus, particularly staphylococcus and gram-negative bacteria,  have been linked to PIGN in adults, especially in developing nations. It has been widely recognized that the prognosis of PIGN is good in children. , But, follow-up studies of biopsy-confirmed adult PIGN have observed progression to end-stage renal disease (ESRD) in 2-34% of the patients.  In this study, we aimed to identify the risk factors that predict poor renal outcome.
| Materials and Methods|| |
A retrospective analysis of 102 patients aged 13-70 years, diagnosed as PIGN by clinical/ biochemical or histological methods or both, during 2009-2011 with at least six months of follow-up was carried out. Patients with persistent low serum complement levels for more than 12 weeks, antinuclear antibody and double stranded DNA positivity at presentation or during follow-up were excluded. Clinical data including antecedent infection, comorbid illness, blood pressure, symptomatology and investigations such as urinalysis, urine spot protein creatinine ratio, serum creatinine, complete blood count, serum anti-streptolysin O (ASO) titer, complement (C3, C4), microbiological cultures and histopathology were analyzed.
Indications for renal biopsy in the study patients included:
- Absence of any two of the following -ASO titer >200 IU/L, recent episode of infection, low serum complement levels.
- Presentation as rapidly progressive glomerulonephritis (RPGN)/anuric renal failure.
- Persistent renal failure (serum creatinine >2 mg/dL) at two weeks.
The renal biopsy specimen was analyzed using light microscopy and immunofluorescence.
Definition of the terms used:
- Nephrotic proteinuria: urine spot protein creatinine ratio >3.5.
- Hypertension: systolic blood pressure (SBP) >140 mm Hg, diastolic blood pressure (DBP) >90 mm Hg.
- Resolution of hypertension: SBP <130 mm Hg and DBP <80 mm Hg.
- Resolution of proteinuria: urine spot protein creatinine ratio <0.2.
- Resolution of hematuria: urine red blood cells (RBCs) <2/hpf
- Full-house immunofluorescence: presence of 2+ or more of IgG, IgM, IgA, C3 and C1q.
- Poor renal outcome: serum creatinine >1.5 mg/dL at 12 months.
| Statistical Analysis|| |
All variables were subjected to univariate analysis by the Fischer Exact test. Statistical significance was assumed at P <0.05. A linear regression model by analysis of variance (ANOVA) was employed for identification of independent risk factors and the logistic regression analysis was employed for risk factor stratification.
| Results|| |
The total number of patients included in this study was 102, with a mean follow-up of 12 months (6-36 months). Of them, 83 patients were biopsy proven (81%) and 21 (19%) were diagnosed by clinical profile and serology alone.
The mean age of the patients was 32.7 ± 15 years (13-70 years). Demographic data and associated comorbidity are given in [Table 1]. Upper respiratory tract infection was the most common antecedent infection and Streptococcus pyogenes was the most common organism isolated in this study. [Table 2] shows the site of infection and organisms associated with PIGN. Peak incidence was noted during the month of September and least in April. Edema and transient oliguria were universally present. About 60% had nephrotic proteinuria (mean urine PCR: 3.67), 14% presented with RPGN and 7% required hemodialysis. Clinical and laboratory data are given in [Table 3].
|Table 1: Demographic data and presence of co-morbidities in the study patients.|
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|Table 2: Site of infection and the organisms grown in the study patients.|
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Renal biopsy was performed in 83 patients. Crescents were present in 15 patients, of whom two had crescentic glomerulonephritis (>50% crescents). Full-house immunofluorescence was the most common pattern (25%) and IgA dominance was seen in 4%. Renal histological findings are given in [Table 4].
Apart from symptomatic treatment with diuretics and anti-hypertensives, 18% of the patients who either presented as RPGN or had crescents in >30% glomeruli received steroid therapy. Of them, 14 patients received intravenous methylprednisolone pulse therapy of 500 mg/d for three days followed by oral steroids 1 mg/kg/day for four weeks and tapered over a period of two months. At the end of 12 months, persistent hypertension was seen in 2% of patients, persistent proteinuria and microhematuria in 10% and persistent renal failure (serum creatinine >1.5 mg/dL) in 11%. Of 86 patients who were not requiring dialysis at presentation, nine (9.5%) developed chronic kidney disease (CKD) (serum creatinine >1.5 mg/dL at three months). Of the seven patients who required dialysis at presentation, five (71.4%) developed CKD. Of them, only one was dialysis dependent after 12 months while the others were in varying stages of CKD. One patient died of non-renal cause during follow-up. In the univariate analysis of all variables by the Fischer Exact test, age >40 years, male gender, serum creatinine >2 mg/dL at one week, comorbid illness, requirement of dialysis, crescents in >30% glomeruli, persistent proteinuria and microscopic hematuria at 12 months had a significant correlation (P <0.05) to serum creatinine >1.5 mg/dL at 12 months. Subjecting these variables to linear regression analysis, serum creatinine >2 mg/dL at one week and persistent proteinuria at 12 months were identified as independent risk factors for poor renal outcome, as shown in [Table 5]. The probability of these factors in predicting poor renal outcome with the logistic regression model was 94.7%. The site of antecedent infection, type of organism, quantum of proteinuria, macrohematuria, oliguria, hypertension, hypo-complementemia at presentation and immuno-fluorescence pattern did not show statistically significant correlation with poor renal outcome.
| Discussion|| |
Miller et al observed that patients died of Bright's disease after scarlet fever in 1849.  Since then, infection has been known to cause GN. Recently, there have been changing trends in various aspects of infection-related GN in adults. The mean age in the present study was 32.7 years, while most other series reported the mean age of the patients to be between 40 and 50 years. , In concurrence with Nasr et al, we found that the most common site of antecedent infection was the upper respiratory tract, and the commonly identified organisms were Streptococcus and Staphylococcus. However, we could not identify the source of infection in 49% of our study patients.
The initial clinical presentation was similar to that described in the literature, with hyper-tension ,, in 74% and macrohematuria in 56% of the patients. Complications like pulmonary edema and hypertensive encephalopathy were present in 7% of the patients. Roy et al  noticed cerebral complications of hypertension including headaches, seizures, mental status changes and visual changes in 30% of the children. The occurrence of nephrotic range proteinuria and low C3 levels were 14- 60% and 43-74%, respectively, in various studies. ,, Acute kidney injury at presentation was documented in 60%. In elderly patients with debilitating conditions, azotemia was seen in 60%, congestive heart failure in 40% and nephrotic syndrome in 20% of the patients studied.  Only 9% of the patients had comorbidities; of them, diabetes was present in three in contrast to other studies where comorbidities like alcoholism, diabetes, drug addiction and obstructive lung disease were present in 38-54% of the patients. ,, Six of nine patients (66%) who had co-morbid illness progressed to CKD in our study. Mazzucco et al  found that PIGN accounted for 9.4% of the cases of non-diabetic glomerular disease in type 2 diabetes.
On renal biopsy, diffuse proliferative GN (70%) was the predominant lesion. Montseny et al  found endocapillary GN in 58%, crescentic GN in 34% and membranoproliferative GN in 7% of their patients. In our study, full-house immunofluorescence was seen in 25%, implying the role of the classical complement pathway also in addition to the alternate pathway. , IgA-dominant immunofluorescence was present in three patients, of whom one had diabetes and staphylococcal infection. IgA-dominant PIGN is a recently recognized morphologic variant that typically occurs in association with staphylococcal infection, commonly seen in elderly and diabetics. , Staphylococcal enterotoxins behave as super antigens that can bind directly to major histo-compatibility complex class II molecules, resulting in massive T cell activation with subsequent cytokine burst and immune complex formation.  Presence of culture-documented staphylococcal infection, hypo-complementemia, endocapillary proliferation with exudetes and sub-epithelial humps on electron microscopy , helps to differentiate from IgA nephropathy.
In this study, steroid therapy was used in 18% of patients. The role of steroids in the treatment of PIGN is controversial. , Generally, it requires only supportive treatment, but corticosteroids or cytotoxic agents might have a role if disease progresses despite eradication of the causative organism as well as in crescentic glomerulonephritis. 
On follow-up, resolution of hypertension occurred earlier than proteinuria and microscopic hematuria, and almost 90% had complete resolution by 6-12 months. Baldwin et al  and Chugh et al  published long-term follow-up of patients with post-streptococcal glomerulo-nephritis for 60 months and 4.5 years, respectively. Irreversible renal disease, as evidenced by hypertension (42%), proteinuria (42%), decreased renal function (38%) or glomerulosclerosis (10%), was reported by the former and persistent hypertension (15%), ESRD (1.9%) and chronic renal failure (3.8%) were observed in the latter study. Only 2% had persistent hypertension in this study. Moroni et al  demonstrated persistent urinary abnormalities in 37%, chronic renal insufficiency in 27% and ESRD in 10% after a follow-up of 7.5 years, whereas it was 10%, 11% and 1%, respectively, in this study. Compared with the available literature, renal outcome in our cohort was better, and this may be due to the younger age of our patients, absence of significant co-morbidities and a shorter duration of follow-up. Risk factors for the progression to CKD include age >40 years, male gender, comorbid illness, requirement of dialysis, >30% crescents on renal biopsy, serum creatinine >2 mg/dL at one week and persistent proteinuria at 12 months, of which the last two factors were found to be independent risk factors.
The long-term prognosis of PIGN in adults is not uniformly good. Hence, it is worthwhile to follow-up periodically all the patients and, in particular, older patients and those with co-morbidities for the occurrence of CKD.
Conflict of interest: Nil
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Dr. Dhanapriya Jeyachandran
Department of Nephrology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]