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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM ASIA-AFRICA  
Year : 2019  |  Volume : 30  |  Issue : 2  |  Page : 492-500
The spectrum of renal diseases observed in native renal biopsies in a single North Indian tertiary care center


1 Department of Medicine, Government Medical College, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Pathology, Government Medical College, Post Graduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

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Date of Submission30-May-2018
Date of Decision13-Jul-2018
Date of Acceptance16-Jul-2018
Date of Web Publication23-Apr-2019
 

   Abstract 


We analyzed the spectrum of biopsy-proven renal disease in a single tertiary care center in North India from 2007 to 2016. A total of 420 biopsies were analyzed. Patients were excluded if clinical details were unavailable or if either the histopathology core or the IF core was inadequate. In the final analysis, 359 biopsies were included. All clinical, laboratory, histopathological, and immunofluorescence (IF) findings were recorded in each case. The usefulness of IF in reaching a definitive diagnosis was also analyzed. The patients were in the age range of 2–94 years; 23.1% were children and 76.9% were adults. Males (60.4%) outnumbered females (39.6%) in all the disease categories except lupus nephritis (LN). Primary glomerular diseases (PGDs) (n = 297, 82.7%) were more common than secondary glomerular diseases (SGDs) (n = 46, 12.8%) and tubulointerstitial diseases (n = 16, 4.5%). The most common PGD was focal segmental glomerulosclerosis (FSGS) (23.4%), followed by minimal change disease (17%) and membranous nephropathy (12.5%), whereas the most common SGD was LN, seen in 9.2%. In the present study, IF helped in reaching the final diagnosis in 44.3%. The entities in which IF was most useful in reaching the final diagnoses were FSGS (31.5%) and IgA nephropathy (14.5%). The final pathological diagnosis correlated with the first clinical possibility in 207 of 359 (57.7%) cases. This 10-year study provides descriptive data and highlights the changing pattern of renal disease possibly due to an increased awareness and referral to higher centers.

How to cite this article:
Sarwal D, D'Cruz S, Singh Punia RP, Minz RW. The spectrum of renal diseases observed in native renal biopsies in a single North Indian tertiary care center. Saudi J Kidney Dis Transpl 2019;30:492-500

How to cite this URL:
Sarwal D, D'Cruz S, Singh Punia RP, Minz RW. The spectrum of renal diseases observed in native renal biopsies in a single North Indian tertiary care center. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 May 24];30:492-500. Available from: http://www.sjkdt.org/text.asp?2019/30/2/492/256856



   Introduction Top


The prevalence of biopsy-proven renal disease (BPRD) varies with geographical regions as well as within the same country and and with demographic factors such as socioeconomic status, age, gender, and race. IgA nephropathy (IgAN) is one of the more common primary glomerular diseases (PGDs) in East Asia[1],[2] as well as in native Europeans and Americans.[3],[4] In contrast, focal segmental glomerulosclerosis (FSGS) is the most common glomerular disease (GD) among African-Americans, South Americans, and in the Middle East.[5],[6],[7]

Indications for biopsy may also vary from one institute to another depending on the protocol in place. The pattern of GD has also changed with time. Renal biopsy is a valuable tool for specific diagnosis of renal disease and assessment of disease activity and is helpful in determining the therapy, disease course, and prognosis. Availability of a definitive diagnosis guides specific therapy of the condition and helps avoid the use of potentially toxic therapies which might not be required in each case.

Common clinical situations in which a renal biopsy is indicated include nephrotic syndrome (NS), nephritic syndrome (N1), rapidly progressive renal failure (RPRF), undiagnosed acute RF, and various systemic diseases with renal involvement.

Most audits of kidney biopsies have been conducted in developed countries,[8] where the relevant determinants of renal disease are much different from those in developing countries. The lack of a renal biopsy registry in India makes it difficult to observe nationwide trends in renal disease over time. However, isolated efforts have been made by a few institutes, and scanty literature is available from North,[9],[10] West,[11] East,[12] and South[13],[14],[15] India. An audit done at a major government center in North India could provide insight into the trends prevalent in this region.

In view of paucity of data from India, we studied the pattern of BPRD in a large tertiary care referral center in North India over the last 10 years (2007–2016) and analyzed the clinicopathological correlation and the extent of benefit afforded by immunofluorescence (IF) in arriving at a final diagnosis.


   Materials and Methods Top


A retrospective audit of all renal biopsies over 10 years (January 1, 2007, to December 31, 2016) was conducted. Relevant patient data were obtained from medical records. For each patient, data on demographics (age and gender), clinical presentation and renal diagnosis on histopathology and IF microscopy were collected. Various histological entities such as PGD and secondary GDs (SGDs) were recorded and subsequently analyzed. The final pathological diagnosis was based on histopathological examination and IF, and the results were correlated with the clinical diagnosis.

A total of 420 real-time ultrasound-guided biopsies were performed, after obtaining a written consent over this period using Bard® 16G biopsy gun by a single operator. Two cores were taken in each case; one core each was sent for histopathological and IF examinations. Patients were observed for 24 hours in the hospital, and any procedure-related complications were noted. All the slides for histopathological examination were stained with hematoxylin and eosin and periodic acid–Schiff stains. Silver stain, Masson’s trichrome, and Congo red stains were used when indicated. Direct IF was done using antibodies against immunoglobulins G, A and M, C3, C1q, and fibrin. A total of 840 cores were obtained. Patients were excluded if clinical details were unavailable or if either the histopathology biopsy core or the IF biopsy core was inadequate. A core was considered adequate if it contained five glomeruli for glomerular lesions and seven glomeruli in cases of tubulointerstitial disease.[16] A total of 61 biopsies were inadequate, and hence, 359 biopsies (718 cores) were available for the final analysis.

Data were recorded in an Excel spreadsheet and then further analyzed. Descriptive statistics was used, and results were expressed as frequencies, percentages, and mean.

Clinical indications for renal biopsy included NS (n = 257, 71.6%), NI (n = 28, 7.8%), asymptomatic urinary abnormalities (AUA) (n = 30, 8.4%), RPRF (n = 22, 6.1%), and unexplained acute kidney injury (AKI) (n = 22, 6.1%). Based on the histopathology and IF findings and the clinical findings, patients were classified into primary and secondary GD. A condition which begins in the glomerulus and causes direct damage to glomerulus was included in primary glomerulopathy, whereas a multisystem disease that also causes glomerulopathy was considered as secondary glomerulopathy.[17] Appropriate tests such as ANA, ANCA, C3, C4, HBsAg, hepatitis C virus, human immunodeficiency virus, and serum and urine electrophoresis were ordered if deemed necessary. Among the PGDs, the prevalence of various histological entities such as minimal change disease (MCD), FSGS, membranoproliferative glomerulonephritis (MPGN), IgAN, membranous nephropathy (MN), crescentic GN, and postinfectious GN were recorded. Similarly, the pattern of SGD such as lupus nephritis (LN), amyloidosis, and drug-induced interstitial nephritis was also looked at.

The prevalence of primary and secondary biopsy-proven renal disease was analyzed separately in the adult (≥19 years) and pediatric (≤18 years) patients. The clinical, histopathological, and IF diagnoses were analyzed to determine the extent to which they correlated with each other, and the role of IF in arriving at final diagnosis was given special attention.


   Results Top


Only patients with adequate biopsies were included. If either the histopathological core or the IF core was inadequate, the patient was excluded. The average number of glomeruli seen in the histopathology core was 13.1, whereas in the IF core, it was 7.7. Out of a total of 420 biopsies (840 cores), 61 biopsies (122 cores) were inadequate and hence not included in the final analysis.

The patients were in the age range of 2–94 years (n = 359). The average age of the entire group was 32.4 years. Patients were further divided into adults and pediatric for subgroup analysis. The average age of the adult group (19–94 years) was 37.9 ± 14.7 years, comprising 76.9% (n = 276) of the study population. The average age of the pediatric group (2–18 years) was 14.3 ± 3.7 years, accounting for 23.1% (n = 83) of the study population.

In the present study, IF helped in reaching the final diagnosis in 159 of 359 cases (44.3%). The entities in which IF was of significant benefit included FSGS (n = 50, 31.5%) and IgAN (n = 23, 14.5%) as depicted in [Table 1].
Table 1: Role of immunofluorescence in reaching the final diagnosis.

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NS (71.6%) was the most common indication for renal biopsy followed by AUA in 8.4%, nephritic syndrome in 7.8%, and RPRF and AKI in 6.1% each among various clinical syndromes. The details of the spectrum of glomerular pathologies seen and their presentation are elaborated in [Table 2].
Table 2: Spectrum of glomerular pathologies in various clinical syndromes.

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In the overall analysis, PGD (n = 297, 82.7%) was more common than SGD (n = 46, 12.8%). Tubulointerstitial diseases were the least common seen in (n = 16, 4.5%) patients. In the total population, males (n = 217, 60.4%) outnumbered females (n = 142, 39.6%) in every disease category except LN, where the M:F ratio was 1:7. In our study population, PGDs were seen more commonly in males [Figure 1]. FSGS (23.4%) was most commonly seen, followed by MCD (17.0%) and MN (12.5%) respectively. LN, seen in 9.2% of the total population under study, was the most frequent SGD seen in our study population [Table 3].
Figure 1: Gender distribution of primary glomerular diseases in the various groups.

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Table 3: Agewise frequencies of biopsy-proven renal diseases.

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In adults, a total of 276 biopsies were adequate. Males comprised 60.1% and females comprised 39.9%. The most common diagnosis was FSGS (23.6%), followed by MN (14.1%) and MCD (11.2%). LN was the most common among SGD (10.1%) [Table 3].

In children, a total of 83 biopsies were adequate, males comprised 61.4% and females 38.6%. The most common diagnosis was MCD (36.1%) followed by FSGS (22.9%) and MN (7.2%) [Table 3]. The proportion of PGD was more in children as compared to adults (89.2% vs. 80.8%). This difference could be attributable to lack of risk factors such as diabetes and chronic hypertension for development of SGD in the pediatric population.


   Discussion Top


This is a 10-year retrospective study from a single tertiary-care referral center in North India. The institution caters to nearby states such as Punjab, Haryana, Himachal Pradesh, Jammu and Kashmir, and Uttar Pradesh. There exist regional differences, as well as a gradual but significant shift in the spectrum of presentation of GD over time, as is seen in registry data from various parts of the world. There is no renal registry in India, and the pattern of renal diseases and changes in their incidence can be derived only from similar studies. As is clear from [Table 4] and [Table 5], even among published studies originating from various centers in India and abroad, there is a variation in the presentation of various GDs.
Table 4: Comparison of our study with other studies across India.

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Table 5: Comparison of our study with other studies globally.

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Renal diseases are caused by a wide variety of insults and may frequently show nonspecific presentations. Hence, renal biopsy assumes importance in achieving a diagnosis where the clinical picture is confounding. Renal biopsy must, however, be done only when deemed necessary as it is associated with some, albeit small, risk.[19] Renal biopsy is an adjunct in the diagnostic armamentarium and cannot be used in isolation.[20] Ideally renal biopsies must be subjected to histopathology (HPE), IF, and electron microscopy (EM) studies for a complete diagnosis to be made. However, due to unavailability and the cost of EM in most centers of the world, it is used only in special circumstances, as was done in our study.

The role of IF in diagnosis cannot be underestimated. In our study, IF contributed to complete diagnosis in 44.3% of cases. It was most useful in FSGS and IgAN [Table 1]. In an earlier study from the same center, light microscopic diagnosis was altered by IF in 6/50 cases (12%).[21] In another study from India, IF helped in reaching the diagnosis in 8.8%.[22]

In the present study, PGDs accounted for 82.7% of all biopsies analyzed. A similar pattern has been reported by other studies as well.[9],[11],[12],[13] LN accounted for 71.7% of all cases of SGDs. There was a male preponderance (60.4%) in all the categories except LN in which, expectedly, the ratio was skewed in favor of females (7:1) [Figure 1].

In the current study, the most common indications for renal biopsy in overall study population were NS (71.6%), followed by AUA (8.4%), NI (7.8%), with RPRF and unexplained AKI in 6.1% each [Table 2]. In most comparable studies from the region and abroad, NS was the most common indication followed by NS; however, in the study from Pakistan,[23] AKI was the second most common indication of renal biopsy [Table 6].
Table 6: Comparison of clinical syndromes in biopsy-proven renal diseases in various studies.

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Overall, FSGS was the most common glomerular pathology, seen in 23.4% biopsies in our study; the pattern was similar in adults (23.6%), whereas in the pediatric population, the most common PGD was MCD, seen in 36.1% [Table 3]. FSGS was also the most common entity seen in another study from Chandigarh,[9] which is different from those reported from Jaipur,[11] Hyderabad,[13] and Kolkata[12] in whom the most common entity was MCD [Table 4].

Comparing our study with the rest of the world, the picture is dramatically different. Like our series, FSGS was also seen most frequently in a large study by Polito et al from Brazil.[5] However, MPGN was the most common entity reported from South Africa,[7] and the most common entity in biopsy-proven glomerular disease was IgAN from China,[1] UK,[8] and Poland[23] [Table 5].

In our study, IgAN was seen in only 8.1% of all cases and accounted for only 2.5% of cases in our pediatric population. In contrast, IgAN is the most common GD in Europe and most of Asia including China, Korea, and Japan.[1],[2],[25] The same is not true for the Indian subcontinent. The difference in the incidence of various GDs could be ascribed to racial factors, prevalent local risk factors such as hepatitis B, C infection, and other dietary factors,[26] and greater population screening and resulting in kidney biopsy of patients with AUA.

LN was the most common SGD seen in 33 patients, accounting for 71.7% of SGD. Class IV lupus was seen in 18 out of 33 (54.5%) biopsies, followed by Class II in 10 out of 33 (30.3%). Our experience is similar to that reported from other studies in our country, where the incidence of LN ranged from 51.1% to 80.1%[9],[11],[12],[13] [Table 4]. Amyloidosis accounted for 10 out of 343 (2.9%) of total biopsies. Amyloidosis was seen in 10 out of 46 patients (21.7%) of SGD. The majority (7 out of 10 cases) of renal amyloid were diagnosed in patients with a past history of tuberculosis. Only three cases out of 10 were primary or AL amyloidosis. This is comparable to other studies from other Indian centers where the incidence ranged from 1.1% to 3.3%.[9],[12],[13] Tubulointerstitial and vascular causes were less prevalent in our series as is seen in other studies with similar indications for biopsy.


   Conclusion Top


The extent to which IF modified the initial histopathological diagnosis reiterates the importance of IF in diagnosis of renal diseases. One of the shortcomings of our study is the inability to perform EM in all cases which would have otherwise helped in better diagnosis. This study provides data on the trends in biopsy-proven renal disease in this part of India. FSGS is fast becoming the most common GD, especially among Indian population and this study corroborates this trend. As India is a vast country with racial, dietary, and cultural heterogeneity, a national kidney biopsy registry data should be set in place to address these regional differences in the spectrum of BPRD.

Conflict of interest: None declared.



 
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Correspondence Address:
Sanjay D'Cruz
Department of Medicine, Government Medical College, Chandigarh
India
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DOI: 10.4103/1319-2442.256856

PMID: 31031385

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