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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2019  |  Volume : 30  |  Issue : 2  |  Page : 445-450
Clinicopathological features and risk factors analysis of IgA nephropathy associated with acute kidney injury: A single-center retrospective study


Department of Nephrology, Gauhati Medical College and Hospital, Guwahati, Assam, India

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Date of Submission08-Jan-2018
Date of Decision09-Oct-2018
Date of Acceptance14-Sep-2018
Date of Web Publication23-Apr-2019
 

   Abstract 


The aim of this study is to investigate the distinctive clinicopathological characteristics of acute kidney injury (AKI) in immunoglobulin A (IgA) nephropathy and identify the possible risk factors for AKI in IgA nephropathy. This study was a hospital-based retrospective analysis of clinicopthological data of IgA nephropathy. The study was conducted in the Department of Nephrology, Gauhati Medical College and Hospital, Assam, India from the period from January 2012 to December 2016. A total of 169 patients who met the inclusion or exclusion criteria were included in the study. Patient data (clinical/demographic and laboratory data including renal biopsy) were collected and were analyzed to assess the risk factors for AKI in IgA nephropathy. For the purpose of analyses, the patients were divided into two groups, AKI (n = 28) and non-AKI group (n = 141). Twenty-eight patients out of 169 developed AKI. The prevalence of AKI in IgA nephropathy patients in our center was 16.5% (28/169). Most AKI patients were hypertensive, hyperlipidemic, had pre-existing impaired kidney function, and higher baseline serum creatinine, higher serum uric acid, and proteinuria, with lower serum albumin and hemoglobin (P <0.05). Use of herbal medications was also significantly more common in the AKI group (P <0.003). Pathological features, like crescents (both cellular and fibrocellular) and interstitial fibrosis/tubular atrophy, were also more severe in the AKI group (P <0.003). In multivariate logistic regression analysis, we found that hypertension, proteinuria, cellular and fibro-cellular crescents, glomerular sclerosis were possible risk factors for AKI. Prevalence of AKI in IgA nephropathy is not as uncommon in north-eastern India as previously thought and knowledge of risk factors for AKI can help in early identification of individuals at risk.

How to cite this article:
Mahanta P J, Agarawalla B, Sharma M. Clinicopathological features and risk factors analysis of IgA nephropathy associated with acute kidney injury: A single-center retrospective study. Saudi J Kidney Dis Transpl 2019;30:445-50

How to cite this URL:
Mahanta P J, Agarawalla B, Sharma M. Clinicopathological features and risk factors analysis of IgA nephropathy associated with acute kidney injury: A single-center retrospective study. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 May 24];30:445-50. Available from: http://www.sjkdt.org/text.asp?2019/30/2/445/256851



   Introduction Top


Immunoglobulin A (IgA) nephropathy is the most common form of glomerulonephritis (GN) worldwide and is characterized by the presence of glomerular immune deposits in which IgA is the dominant class of Ig detected by immunofluorescence (IF).[1] Its distribution varies in different geographic regions, being the most common form of primary GN in Asia (30%–50%), very common in Europe, less common in North America, and least common in South America and Africa.[2] IgA nephropathy occurs at all ages, but is most common in the second and third decades of life, and much more common in males than females. Most common clinical presentation is episodic macroscopic hematuria (40%–50%) usually after an intercurrent mucosal infection, typically in the upper respiratory tract or gastrointestinal tract, other presentation includes asymptomatic hematuria and proteinuria in 30-40% of cases, 5% of cases can have nephrotic presentation, and only <5% cases present with acute kidney injury (AKI).

AKI can occur because of the following mechanisms. First, it can be due to acute severe immune and inflammatory injury with necrotizing GN and crescent formation (crescentic IgA nephropathy). Alternatively, AKI can occur with mild glomerular injury when heavy glomerular hematuria leads to tubule occlusion by red blood cells (RBCs). Third, especially in elderly patients, chronic IgA nephropathy will predispose to AKI from a variety of incidental renal insults.[3],[4],[5]

Understanding the epidemiological features and the associated risk factors would help greatly in the identification of AKI in IgA nephropathy. Previous studies focused more on macroscopic hematuria-related AKI rather than clinical and pathological risk factors.[6],[7],[8] In this study, we summarize the clinical and pathological characteristics of IgA nephropathy that are associated with AKI and try to identify the possible risk factors for AKI in the IgA nephropathy patients.


   Materials and Methods Top


This study was a hospital-based retrospective analysis of clinicopathological data of IgA nephropathy. The study was conducted in the Department of Nephrology, Gauhati Medical College and Hospital, Assam, India from the period of January 2012 to December 2016. A total of 169 cases of IgA nephropathy who met the inclusion or exclusion criteria were included in the study. Patient data (clinical/demographic and laboratory data including renal biopsy) were collected and were analyzed to assess the risk factors for AKI in IgA nephropathy. For the purpose of analyses the patients were divided into two groups, AKI (n = 28) and non-AKI group (n = 141).

All the cases of AKI were managed with the intention to treat and details of which were as follows: two patients had crescentic GN managed with methyl prednisolone (MP) pulse followed by oral steroid and injectable cyclophosphamide. Four patients had acute tubular necrosis (ATN) with RBC cast, managed conservatively with hydration. Five patients had ATN without RBC cast, probably due to sepsis, managed conservatively with antibiotic and others. Seven patients had acute tubulointerstitial nephritis (ATIN), probably herbal medicine induced and were managed conservatively. Two had changes suggestive of malignant hypertension (HTN), managed with adequate pressure control and were evaluated to rule out other causes. In eight patients, we could not detect the exact cause, but once we ruled out infection, we treated them with MP pulse therapy.

Inclusion criteria

All biopsy-proven primary IgAN were included in the study.

Exclusion criteria

Patients with secondary IgA nephropathy (Henoch-Schonlein purpura, systemic lupus erythematosus, and hepatitis B) and posttransplant IgA nephropathy were excluded from the study.

The definition and categories of AKI was as per the 2012 KDIGO criteria.[9] HTN, which defined as a repeatedly elevated blood pressure exceeding 140 over 80 mm Hg, a systolic pressure >140 or a diastolic pressure above 80 mm Hg. Anemia was defined when hemoglobin <110 g/L for females, and <120 g/L for males.


   Statistical Analysis Top


Results of continuous variables are summarized with mean ± standard deviation. For categorical variables, the results were expressed as frequencies and percentages. Continuous data were compared using the Student’s t-test; proportions were compared with the Chi-square test or Fisher’s test. Multivariate logistic regression was used to identify correlates of AKI and variables that were clinicopathological relevant base on professional knowledge in univariate analysis. Variables with P <0.05 in univariate analysis for a relationship with AKI were entered into multivariate analysis as covariates. Results are presented as odds ratios (ORs) with 95% confidence interval (CI). All tests were two-sided and P <0.05 was considered to be statistically significant. The Statistical Package for Social Sciences version 25.0 (IBM Corp., Armonk, NY, USA) was used for calculation of statistical data.


   Results Top


During the study period, January 2012 to December 2016, out of 169 patients diagnosed with primary IgA nephropathy in our center 28 patients fulfilled the criteria of AKI. Thus, the prevalence of AKI in IgA nephropathy in this study is 16.56%. There were 14 (50%), five (17.85%), and nine (32.14%) patients in AKI stage I, II, and III, respectively. Mean baseline versus peak serum creatinine in AKI staging I, I, III was 1.28 mg versus 2.8; 1.4 versus 4.5; 2.1 versus 11.11, respectively. Of 28 patients with AKI, 13 patients of IgA nephropathy had AKI as their first presentation.

Of these 13 patients, 10 patients were in stage 1 and 3 patients were in stage II AKI.

Mean age of patients who developed AKI was 31.3 ± 10.3 years and 46% of them are males. Patients who developed AKI were older, more commonly smoker and had macroscopic hematuria (though this difference is not significant) and significantly more frequently anemic and hypertensive [Table 1].
Table 1: Demographics and clinical features.

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AKI group had more patients with preexisting renal failure (P <0.01) and higher baseline serum creatinine (P <0.001), had more patients with proteinuria (>1 g/day) though not significant. AKI group had higher uric acid (P <0.0001), lower serum albumin (P <0.04), higher total cholesterol (P <0.001), and triglyceride (P <0.08) [Table 2].
Table 2: Laboratory parameters.

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When pathological features were compared, it was found that AKI group had more glomeruli with crescents (P <0.001), less mesangial proliferation (P <0.001), more endothelial proliferation (P <0.85), more glomeruli with segmental sclerosis (P <0.001), and more interstitial fibrosis and tubular atrophy (P <0.001) [Table 3].
Table 3: Pathological features.

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Factors strongly associated with AKI includes pre-existing renal failure, HTN, proteinuria and herbal medicine intake and histological features such as the presence of crescents, glomerulosclerosis, and interstitial fibrosis and tubular atrophy ≥50% [Table 4].
Table 4: Risk factors for AKI.

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   Discussion Top


The prevalence of AKI in IgA nephropathy in previous published studies varies widely from <5%[7] to >27%.[3] In the study, the prevalence of AKI in IgA nephropathy is 16.5%. In this study, we had analyzed in details the clinical and pathological characteristics of AKI in IgA nephropathy and had tried to identify the risk factors for AKI. The mean age of patients who developed AKI in the study was 31.3 ± 10.3 years [Table 1]. According to previous studies by Zhang et al, older age is a risk factor for developing AKI in IgA nephropathy,[10] but in our study as already mentioned mean age was 31.3 years, thus the possibility of older age as a risk factor for AKI cannot be ruled out also in our study. We did not find any significant difference between the mean age of AKI and non-AKI-group (P = 0.24). Furthermore in our study, sex distribution was similar in both the groups and male sex was not a risk factor for AKI [Table 2].

One of the important risk factors identified in our study was pre-existing renal failure (OR 4.3, 95% CI 1.8, 10.1). As compared to 19.8% in non-AKI group, 53.5% had pre-existing impaired renal function in AKI group (P <0.01) [Table 2]. Baseline serum creatinine in AKI group was significantly higher than non-AKI group (P <0.001) [Table 2]. Other important risk factors include hypertension, proteinuria, and macroscopic hematuria [Table 4]. About 67.9% of patients of AKI group were hypertensives as compared to 39% of non-AKI group. The mean systolic and diastolic blood pressure in the AKI group (144.3 ± 19.8, 89.4 ± 13.3) is significantly higher than the non-AKI group (132 ± 17.7, 74.5 ± 10) [Table 2]. Furthermore, AKI group had significantly higher serum uric acid, higher total cholesterol, and lower serum albumin and hemoglobin [Table 2]. Similar clinical changes were seen in AKI-IgAN subgroup in studies by Wen et al[11] and Zhang et al[10] as compared with non-AKI counterpart.

On the evaluation of the pathological features, we found that AKI group had significantly higher proportions of crescents, global glomerulosclerosis, segmental glomerulosclerosis, interstitial fibrosis, and tubular atrophy [Table 3]. On multivariate analysis interstitial fibrosis, tubular atrophy (≥50%) (OR 5.16 95% CI 0.93, 28.56) and glomerulosclerosis (≥50%) (OR 4.27 95% CI 0.76, 24.3%) were the most important histological risk factors for the development of AKI in IgA nephropathy [Table 5].
Table 5: Multivariate analysis.

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Similar findings were also observed in studies by Zhang et al[10] and Chen et al.[12] Other important finding in this study was the strong association of herbal/indigenous medicine intake with development of AKI (OR 3.65, 95% CI 1.11, 12.05) [Table 5]. This association was also reflected in histological changes, where almost 40% had features of ATIN or ATN (without RBC cast in tubules) [Figure 1]. This finding is very important in the sense that it is completely preventable with proper patient education. Intake of these herbal medicines is very common in this area because of low cost and easy availability. And if patients are properly counseled about the ill effects of these toxins, the incidence of AKI can be reduced.
Figure 1: Diagram of pathological changes in IgAN associated AKI.
GN: Glomerulonephritis, ATN: Acute tubular necrosis, RBC: Red blood cell, ATIN: Acute tubulointerstitial nephritis, IgAN: Immunoglobulin A nephropathy, AKI: Acute kidney injury.


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When we study the pathological characteristics of those cases who developed AKI we found that 14% of patients had ATN with RBC cast, which was probably due to macroscopic hematuria. Another 18% had ATN without RBC cast and 25% had ATIN, these histological changes can be due to herbal medicine intake. Twenty-nine percentage cases had nonspecific finding which cannot be explained by any particular pathogenic mechanism [Figure 1].

There are a few limitations in this study, first is the small sample size. A study with a larger sample size can give more insight into the epidemiology and risk factors of AKI in IgAN. Furthermore, this study is a single-center retrospective study, and a retrospective study depends on records, which may be incomplete. Third, our institute is a tertiary care center and few milder cases of AKI may not get referred to our institute and thus, the prevalence of AKI may be underestimated.


   Conclusion Top


AKI–IgA nephropathy is relatively common in this region of India. Patients who developed AKI are more frequently hypertensive, anemic, hypoalbuminemic, dyslipidemic, had higher serum uric acid and had higher baseline serum creatinine. Measures such as control of blood pressure, dyslipidemia, and control of serum uric acid level may have a role in lowering of the prevalence of AKI.

Conflict of interest: None declared.



 
   References Top

1.
D’Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med 1987;64:709-27.  Back to cited text no. 1
    
2.
McGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide: A systematic review of the literature. Nephrol Dial Transplant 2011;26:414-30.  Back to cited text no. 2
    
3.
Rivera F, López-Gómez JM, Pérez-García R; Spanish Registry of Glomerulonephritis. Clinicopathologic correlations of renal pathology in Spain. Kidney Int 2004;66:898-904.  Back to cited text no. 3
    
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Cerdá J, Lameire N, Eggers P, Pannu N, Uchino S, Wang H, et al. Epidemiology of acute kidney injury. Clin J Am Soc Nephrol 2008;3:881-6.  Back to cited text no. 4
    
5.
Lameire NH, Bagga A, Cruz D, et al. Acute kidney injury: An increasing global concern. Lancet 2013;382:170-9.  Back to cited text no. 5
    
6.
Praga M, Gutierrez-Millet V, Navas JJ, et al. Acute worsening of renal function during episodes of macroscopic hematuria in IgA nephropathy. Kidney Int 1985;28:69-74.  Back to cited text no. 6
    
7.
Kveder R, Lindic J, Ales A, Kovac D, Vizjak A, Ferluga D. Acute kidney injury in immunoglobulin A nephropathy: Potential role of macroscopic hematuria and acute tubulointerstitial injury. Ther Apher Dial 2009;13: 273-7.  Back to cited text no. 7
    
8.
Moreno JA, Martín-Cleary C, Gutiérrez E, et al. AKI associated with macroscopic glomerular hematuria: Clinical and pathophysiologic consequences. Clin J Am Soc Nephrol 2012; 7:175-84.  Back to cited text no. 8
    
9.
Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012;120:c179-84.  Back to cited text no. 9
    
10.
Zhang L, Li J, Yang S, et al. Clinico-pathological features and risk factors analysis of IgA nephropathy associated with acute kidney injury. Ren Fail 2016;38:799-805.  Back to cited text no. 10
    
11.
Wen YK, Chen ML. The spectrum of acute renal failure in IgA nephropathy. Ren Fail 2010;32:428-33.  Back to cited text no. 11
    
12.
Chen MG, Ye XH, Liang HY, Yang Q. Clinical and pathological analysis of IgA nephropathy with acute kidney injury. Zhonghua Er Ke Za Zhi 2016;54:610-3.  Back to cited text no. 12
    

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Correspondence Address:
Bishal Agarawalla
Department of Nephrology, Gauhati Medical College and Hospital, Guwahati - 781 032, Assam
India
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DOI: 10.4103/1319-2442.256851

PMID: 31031380

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