A Clinicopathologic Study of Glomerular Disease: A Single-Center, Ten-year Retrospective Study from Northwest India

doi:10.21203/rs.3.rs-4438079/v1

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A Clinicopathologic Study of Glomerular Disease: A Single-Center, Ten-year Retrospective Study from Northwest India

https://doi.org/10.21203/rs.3.rs-4438079/v1

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Studies published from centers across India have reported different and contradicting patterns of glomerular disease. In this retrospective study, we report our experience from a Tertiary Care Center in Northwest India. A total of 1186 renal biopsies performed between 2014 and 2023 were reviewed of which 632 were excluded from the study because the biopsies were taken from an allograft. The study included 332 males (59.92%) and 222 females (40.07%) with an age range of 08–82 years (mean 40.34 ± 5.04 years). Majority of the biopsies (99.07%) showed some form of glomerulonephritis (GN), either primary (68.88%) or secondary glomerular disease (SGD) (31.12%). Membranous nephropathy was the most common type of primary GN (24.73% of primary GN), followed by focal and segmental glomerulosclerosis (FSGS); 20.96% of primary GN) and minimal change disease (MCD; 17.47% of primary GN).Amyloidosis was the most frequent SGD (44.64% of secondary GN). Lupus nephritis(LN) was found in 32.14% and TMA(Thrombotic microangiopathy) in 17.85%.

Glomerular disease is a common cause of end stage renal disease in both developing and developed countries. The prevalence of glomerular disease is different in various regions of the world and varies depending on the race, age, geographical, etiological, cultural, and economic characteristics.^1–4 Moreover, the pattern of glomerular disease varies in different geographical regions within the same country and has been reported to change with time.^3–7 A kidney biopsy is needed for the correct characterization of various types of glomerular diseases.

National Renal Biopsy Registries are available in the developed countries which depict the pattern of glomerular disease most commonly encountered. Unfortunately, we do not have a National Registry, and there is scattered data on the prevalence of glomerular diseases from different parts of India with none available from Rajasthan, which is the largest state in India and is mostly comprised by arid and inhospitable Thar Desert. Minimal change disease (MCD) has been reported to be the most common cause of glomerular disease in Northern India,^8,9 whereas immunoglobulin A nephropathy (IgAN) has been found to be more common in Western India.¹⁰ A recent study from North India compared the profile of glomerular disease at their center across five decades and found a change in the trend of glomerular diseases. They found that focal and segmental glomerulosclerosis (FSGS) followed by membranous nephropathy (MN) were the most common pathologies seen.⁷ Non-IgA mesangial proliferative glomerulonephritis (MesPGN) followed by FSGS were the predominant pathologies reported from South India.⁶ In another study from South India, the most common primary glomerular disease (PGD) reported was MCD.¹¹ A tertiary center from Eastern India too reported MCD as the most common PGD encountered.¹² Since there are differences in the reports of glomerular diseases from different parts of the world and from within the same country, the current study was performed to show the frequency of occurrence of primary and secondary glomerulonephritis (GN) observed in a Tertiary Care Hospital Catering to patients from Rajasthan and adjoining states.

MCD followed by FSGS followed by diffuse proliferative GN were the most common entities in individuals < 20 years of age. In the 20–39 years age group, MN was the most common pathology seen. MN was again the most common pathology seen in patients aged above 40 years followed by Amyloidosis and followed by FSGS. In this study, MN was the most common primary GN observed overall from this part of India & was the most common GN in individuals above 20 years of age presenting with the nephrotic syndrome. The geographical and regional differences in the pattern of GNs point to the necessity of having a central biopsy registry.Glomerular disease is a common cause of end stage renal disease in both developing and developed countries.

Since there are differences in the reports of glomerular diseases from different parts of the world and from within the same country, the current study was performed to show the frequency of occurrence of primary and secondary glomerulonephritis (GN) observed in a Tertiary Care Hospital Catering to patients from Rajasthan and adjoining states.

The patients referred to the Nephrology Department at the Mahatma Gandhi University Of Medical Sciences And Technology, Jaipur, Rajasthan, and who were subjected to kidney biopsy, from 2013 to 2023, constituted the subjects of this study. A total of 1186 renal biopsies were performed in this period out of which 632 (53.28%) were on transplanted subjects which were not included in the study.The percutaneous technique with ultrasound guidance using Tru-Cut 14-gauge needles and Bard® disposable core biopsy instrument (Bard Biopsy Systems® ) was used for all biopsies.In most of the cases, two cores were obtained; one specimen was fixed in formalin to be evaluated under light microscopy and the other sent for immunofluorescence studies. Paraffin sections were prepared and stained with hematoxylin and eosin, periodic acid-Schiff, Masson trichrome, Congo red, and Jones silver methenamine stains. All the renal biopsies were examined by a pathologist and evaluated with light microscopy and immunofluorescence(using IgA, IgG, IgM, IgE, C3, and C4).

The indications for biopsy included: nephrotic syndrome (NS), proteinuria more than 1 g/day with active urine sediment, systemic disease with renal involvement, and unexplained renal insufficiency.Glomerular pathologies were classified into the following:

Primary glomerular diseases (PGD): IgAN, FSGS, MN, MCD,membranoproliferative GN (MPGN),diffuse proliferative GN (DPGN), MesPGN,and crescentic GN (CresGN).

Secondary glomerular diseases (SGD):Lupus nephritis (LN), GN related to hepatitis B or C, systemic vasculitides, Henoch Schönlein purpura, diabetic nephropathy(DN), and amyloidosis.

Tubulointerstitial nephropathies (TIN),including acute TIN and chronic TIN Vascular nephropathies including benign and malignant nephrosclerosis and thrombotic microangiopathies.

Significant clinical data were gathered from the patients’ medical files, including the following: clinical diagnosis, serum creatinine, 24 h proteinuria, presence of hematuria, and presence of hypertension.Complications of renal biopsy were also noted. Severe complications were defined as severe renal bleeding requiring blood transfusions,acute kidney injury (AKI) from obstruction with blood clots, urosepsis, and death.^12,13 Clinical syndromes were categorized into NS, acute nephritic syndrome, rapidly progressive GN,asymptomatic urinary abnormalities, AKI, and chronic kidney disease(CKD).

Of the 554 cases studied, 332 were male (59.9.2%) & 222 were female(40.07%).Their age ranged from 08 to 82 years with a mean of 40.34 ± 5.04 years. The frequency of presenting clinical syndromes among the individuals undergoing kidney biopsy is shown in Fig. 1.NS was the indication for biopsy in two-thirds of the total biopsied sample.The types of renal disease found on biopsy are shown in Fig. 2. Majority (84.3%) of the biopsies showed some form of GN, either PGD (58.3%) or SGD (26.0%). Isolated tubulointerstitial disease(TID) ,& vascular pathologies were seen less frequently.

There were 323 cases (58.3%) of PGD. MN was the most common type of primary GN observed in 82 cases (25.38% of PGDs), followed by FSGS (68 cases, 21.05%) and MCD (55 cases, 17.02%). IgAN & CresGN was found in 5.41% of cases each (30 cases each), DPGN in 3.97% (22 cases),MPGN in 2.88% (16 cases), chronic sclerosing GN(CSGN) in 2.34% (13 cases), MesPGN in 1.08%(07 cases).

MCD was also the most prevalent PGD encountered in females, seen in 25 out of 323 cases (07.73%) and FSGS was also at the same position, followed by MN (23, 7.12%), CresGN (15, 4.64%), DPGN (09, 2.78%), IgAN(08, 2.47%), MPGN (07,2.17%), CSGN (06,1.85%), and finally MesPGN (04,1.23%). IgAN was more common in males (6.81% vs 2.47%) and MesPGN appeared to be more common in females (1.23% vs.0.92%).Of the SGDs (144 cases, constituting 25.99% of the total biopsies), Amyloidosis was the most frequently diagnosed disease (75 cases, 52.08% of SGDs).LN was found in 54 cases (37.5%) and diabetic glomerulosclerosis was found in six cases (4.16%). LN was the most common diagnosis in females in both PGDs and SGDs(seen in 19.36% of females).

The overall frequencies of different renal diseases in native renal biopsies together with some basic data for each disease are shown in Table 1. MN was the most common pathology seen overall (14.80%) followed by Amyloidosis(13.53) followed by FSGS (12.27%).

Table 2 shows the underlying clinical syndrome in each histological category. It is obvious from the table that the most frequent causes of NS were MN, FSGS, and MCD. Of note, 17.48% of patients with Amyloidosis and 4.89% of patients with LN presented with NS.

There was a difference in the prevalence of glomerular diseases according to different age groups (Table 3). MCD (27.10% of cases) followed by FSGS (17.75%) and DPGN (13.08%) were the most common pathology in individuals below 20 years of age. In the 20–39 years group, MGN (13.77%), TMA (12.44%), and LN (12%) were the most common pathologies seen. MGN (22.07%) was again the most common pathology seen in patients aged above 40 years followed by amyloidosis (21.17%) and FSGS (12.61%). TMA was the most common secondary GN in patients < 40 years and amyloidosis in those > 40 years of age.

This study is a single-center 10-year retrospective study from Northwest India. The Mahatma Gandhi University Of Medical Sciences & Technology is the reknown Tertiary Referral Center of the state and also caters to nearby states such as Punjab, Uttar Pradesh, and Haryana. Data prior to the period was not analyzed due to poor records and nonstandardization of biopsy reporting.In the present study, PGDs accounted for 58.3% of all biopsies were performed. Overall, MN was the most common glomerular pathology encountered & was the most common histology seen in patients with age above 20 years.

Among the secondary GNs, Amyloidosis was the most common pathology seen. Table 4 lists the findings from our study as compared with other studies from India and neighboring countries.PGD was the most predominant renal disease in our study, as well as in other recent studies.^{(3,5,7,11,12)} Several studies have shown a decline in the relative frequency of MCD.^{(1,4,6,7,14,15)} However, in our study, MN was the most common PGD. Table 5 shows the common glomerular diseases encountered in the present study as compared with patterns from countries other than India.^{(1,3,16–20)}

MN was the most commonly seen pathology in patients aged above 20 years, which is a deviation from the trend observed from other studies from India. A recent study from North India also reported MN to be the most common glomerular pathology in individuals older than 40 years.⁷ In addition, MN was the most common pathology seen in a study from Nepal¹⁴ and China.²⁰ In our study, IgAN was seen only in 5.41% of all cases but accounted for 10.22% of cases in the 20–39 years age group. IgAN is the most common glomerular disease in Europe and most of Asia including China, Korea, and Japan.²¹ The same is not true for the Indian subcontinent. Studies from Pakistan and India have reported the prevalence of IgAN to be between 1.5% and 8.6%^6,7,11,12,15 as was seen in our study.Among the SGD, Amyloidosis and LN were common constituting 52.08% and 37.5%, respectively. LN is the most common SGD worldwide across America, Europe, Asia, and the Middle East.²¹ LN is also the most common SGD seen in the Indian subcontinent.^{6,7,11,12,14,15} but in present study Amyloidosis is the most common SGD.Amyloidosis accounted for 13.53% of total biopsies and 52.08% of those with SGD. The majority of renal amyloid cases were diagnosed on renal biopsies from patients with a history of tuberculosis. Only seven cases out of 75 were primary or AL amyloidosis.two out of these seven cases diagnosed with multiple myeloma.

90.67 percent of cases of amyloidosis were classified as secondary (AA) amyloid. India,with an incidence greater than two million, has the highest number of new cases of TB annually in the world.²² High rates of secondary amyloidosis in our series are probable since tuberculosis is endemic in this region. DN was found in only 1.08% of SGN cases. This may be because of the practice patterns that diabetics are usually not biopsied unless there is doubt about diabetes being the cause of renal disease.Tubulointerstitial and vascular causes were less prevalent in our series as is seen in other studies with similar indications for biopsy.

Table 1

Frequency distribution and epidemiologic and clinical data of primary and secondary glomerulonephritides.
Disease	Patients n(%)	Age(year) mean ± SD	Male n(%)	Female n(%)	Clinical picture
Disease	Patients n(%)	Age(year) mean ± SD	Male n(%)	Female n(%)	Nephrotic range proteinuria (%)	Hypertension (%)	Hematuria (%)	Elevated creatinine (> 1.5 mg/dL) (%)
Primary GN MCD FSGS MN MPGN IgAN MesPGN CrescenticGN DPGN CSGN	55(9.92) 68(12.27) 82(14.80) 16(2.88) 30(5.41) 7(1.08) 30(5.41) 22(3.97) 13(2.34)	29.88 ± 18.96 38.74 ± 11.51 42.73 ± 13.23 25.65 ± 11.95 30.74 ± 17.04 45.88 ± 8.84 48.25 ± 11.69 30.67 ± 13.63 34.75 ± 15.78	30(54.54) 43(63.23) 59(71.95) 09(56.25) 22(73.33) 03(42.85) 15(50.00) 13(59.09) 07(53.84)	25(45.45) 25(36.76) 23(28.04) 07(43.75) 08(26.66) 04(57.14) 15(50.00) 09(40.90) 06(46.15)	84.67 70.59 73.45 60.59 10.09 23.09 15.59 18.90 30.09	04.46 32.39 25.29 50.10 15.54 12.24 70.24 80.10 70.0	07.78 30.40 22.29 82.29 100.0 90.0 100.0 100.0 52.40	3.90 30.09 12.21 28.89 26.78 12.29 90.09 72.29 100.0
SecondaryGN Amyloidosis DN LN Hypertensive nephrosclerosis	75(13.53) 6(1.08) 54(9.74) 9(1.62)	51.35 ± 13.86 57.25 ± 5.5 28.30 ± 18.92 59.00 ± 9.08	48(64.00) 04(66.66) 11(20.37) 06(66.66)	27(36.00) 02(33.33) 43(79.62) 03(33.33)	78.80 44.48 42.90 22.25	19.90 100.0 50.7 100.0	19.90 45.00 68.89 25.00	48.6 22.25 76.7 100.0
Others ATN AIN CIN ACN TMA	12(2.16) 5(0.90) 11(1.98) 08(1.44) 51(9.20)	38.79 ± 11.15 37.60 ± 14.82 43.75 ± 7.54 35.33 ± 10.44 37.67 ± 09.04	05(41.66) 02(40) 06(54.54) 02(25.00) 43(84.31)	07(58.33) 03(60) 05(45.45) 06(75.00) 08(15.68)	- - - - -	32.28 18.90 76.09 100.0 100.0	20.09 19.90 01.00 35.50 100.0	100.0 100.0 100.0 100.0 100.0

SD:Standard deviation, MCD:Minimal change disease, FSGS:Focal segmental glomerulosclerosis, MN: Membranous nephropathy, MPGN:Membranoproliferative glomerulonephritis, MesPGN:Mesangial proliferative glomerulonephritis, DPGN:Diffuse proliferative glomerulonephritis, IgAN:Immunoglobulin A nephropathy, CSGN:Chronic sclerosing glomerulonephritis, LN:Lupus nephritis, DN:Diabetic nephropathy, ATN:Acute tubular necrosis, AIN:Acute interstitial nephritis, CIN:Chronic tubulointerstitial nephritis, ACN: Acute cortical necrosis, TMA:Thrombotic microangiopathy.

Table 2

Frequency of histological diagnosis on the basis of clinical syndromes.
Renal disease	No.	NS(%)	AGN(%)	RPRF(%)	AUA(%)	AKI(%)	CKD(%)
MCD	55	51(17.83)	04(12.12)	-	-	-	-
FSGS	68	65(22.72)	03(9.09)	-	-	-	-
MN	82	78(27.27)	-	-	04(12.12)	-	-
MPGN	16	11(03.84)	02(6.06)	01(0.86)	01(3.03)	-	01(1.85)
IgAN	30	09(03.14)	10(30.30)	01(0.86)	10(30.30)	-	-
MesPGN	07	04(1.39)	01(3.03)	02(173)	-	-	-
Crescentic GN	30	-	02(6.06)	28(24.34)	-	-	-
DPGN	22	02(0.69)	01(3.03)	08(06.95)	-	-	-
CSGN	13	01(0.34)	-	04(3.47)	-	-	08(14.81)
Amyloidosis	75	50(17.48)	-	-	16(48.48)	-	09(16.66)
DN	06	01(0.34)	-	-	02(6.06)	-	01(1.85)
LN	54	14(04.89)	10(30.30)	23(20.00)	-	03(15.00)	04(07.40)
Hypertensive nephroslecrosis	09	-	-	-	-	-	09(16.66)
ATN	12	-	-	-	-	-	12(22.22)
AIN	05	-	-	1(0.86)	-	04(20.00)
CIN	11	-	-		-	02(10.00)	09(16.66)
ACN	08	-	-		-	07(35.00)	01(1.85)
TMA	51	-	-	47(40.86)	-	04(20.00)

NS:Nephrotic syndrome,AGN:Acute glomerulonephritis,RPRF:Rapidly progressive renal failure, AUA:Asymptomatic urinary abnormality,AKI:Acute kidney injury,CKD:Chronic kidney disease, MCD:Minimal change disease,FSGS:Focal segmental glomerulosclerosis,MN:Membranous

nephropathy,MPGN:Membranoproliferative glomerulonephritis,MesPGN:Mesangial proliferative glomerulonephritis,DPGN:Diffuse proliferative glomerulonephritis,IgAN:Immunoglobulin A nephropathy,CSGN:Chronic sclerosing glomerulonephritis,LN:Lupus nephritis,DN:Diabetic nephropathy,ATN:Acute tubular necrosis,AIN:Acute interstitial nephritis,CIN:Chronic tubulointerstitial nephritis,ACN: Acute cortical necrosis,TMA: Thrombotic microangiopathy.

Table 3

Distribution of primary and secondary glomerular disease in different age groups.
Glomerular disease	Number	Age(years)
		< 20(n = 107)	20–39(n = 225)	≥ 40(n = 222)
MCD	55	29(27.10%)	16(7.11%)	10(4.50%)
FSGS	68	19(17.75%)	21(9.33%)	28(12.61)
MN	82	02(1.86%)	31(13.77%)	49(22.07)
MPGN	16	04(3.73%)	08(3.55%)	04(1.80)
IgAN	30	03(2.80%)	23(10.22%)	04(1.80)
MesPGN	07	01(0.93%)	04(1.77%)	02(0.90)
Crescentic GN	30	04(3.73%)	20(8.88%)	06(2.70)
DPGN	22	14(13.08%)	06(2.66%)	02(0.90)
CSGN	13	02(1.86%)	03(1.33%)	08(3.60)
Amyloidosis	75	04(3.73%)	24(10.66%)	47(21.17)
DN	06	-	-	06(2.70)
LN	54	06(5.60%)	27(12.00%)	21(9.45)
Hypertensive nephrosclerosis	09	-	-	09(4.05)
ATN	12	03(2.80%)	05(2.22%)	04(1.80)
AIN	05	01(0.93%)	03(1.33%)	01(0.45)
CIN	11	-	03(1.33%)	08(3.60)
ACN	08	03(2.80%)	03(1.33%)	02(0.90)
TMA	51	12(11.21%)	28(12.44%)	11(4.95)

MCD:Minimal change disease,FSGS:Focal segmental glomerulosclerosis,MN:Membranous nephropathy,MPGN:Membranoproliferative glomerulonephritis,MesPGN:Mesangial proliferative glomerulonephritis,DPGN:Diffuse proliferative glomerulonephritis,IgAN:Immunoglobulin A nephropathy,CSGN:Chronic sclerosing glomerulonephritis,LN:Lupus nephritis,DN:Diabetic nephropathy.

Table 4

Comparison of spectrum of glomerular disease seen in our study with other studies in India and neighboring countries.
Parameter	Present study	SMS,Jaipur²³	PGIMER, Chandigarh⁷	IPGMER, Kolkata¹²	NIMS,Hyderabad¹¹	CMC, Vellore⁶	Pakistan¹⁵	Nepal ¹⁴
Period	2013–2023	2008–2013	2002–2007	2010–2012	1990–2008	1990–2001	1995–2008	2001–2007
Number of biopsies	554	622	364	666	1849	3703	1793	137
PGD	58.30	79.4	89	79.13	69.1	-	73	-
SGD	25.99	14.5	11	20.87	18.2	-	10.9	-
MCD	9.92	21.1	14.8	20.12	15.1	11.8	5.8	10.2
FSGS	12.27	10.5	30.6	18.02	10.5	18.28	21.2	8
MN	14.80	15.0	24.4	12.01	7	9.8	17.2	42.3
MPGN	2.88	9.6	17.9	5.25	3.9	3.7	1.1	21.9
IgAN	5.41	7.4	1.8	8.1	4.4	8.6	1.5	2.9
MesPGN	1.26	6.4	-	0.6	5.2	20.2	1.9	1.5
CrescenticGN	5.41	2.6	3.6	7.51	4.5	7.91	5.2	-
DPGN	3.97	5.3	2.8	4.95	10.3	14.66	3.9	2.2
CSGN	2.34	1.9	3.7	3	6.7	4.62	11.6	2.2
Amyloid	13.53	5.9	3.3	1.2	1.5	1.11	4.6	1.5
DN	1.08	0.6	0.2	0.3	1.2	2.99	0.9	-
LN	9.74	7.6	6.8	15.32	14.6	7.53	4.9	1.5

Table 5

Prevalence of primary glomerular diseases compared to that reported in other countries.
Glomerular disease	Present study	Saudi Arabia¹⁶	Bahrain¹⁷	Korea¹	Czech Republic¹⁸	China¹⁹	Iraq²⁰
MCD	9.92	11.5	30	15.5	12.4	20.4	17.1
FSGS	12.27	21.3	23.8	5.6	10.8	-	26.3
MN	14.80	10.6	-	12.3	9.3	20.7	14.5
MPGN	2.88	20.7	14.3	4	-	-	16.2
IgAN	5.41	6.5	-	28.3	34.5	10.5	-
MesPGN	1.26	16.3	-	-	11.3	7.88	22.5

MCD: Minimal change disease, FSGS: Focal segmental glomerulosclerosis, MN: Membranous nephropathy, MPGN: Membranoproliferative glomerulonephritis, IgAN: Immunoglobulin A nephropathy, MesPGN: Mesangial proliferative glomerulonephritis.

The spectrum of glomerular disease differs according to age, race, and geographical regions.The pattern of biopsy-proven renal disease differs between different regions of the same country. We found MN to be the most common cause of GN overall and even in individuals above 20 year, while MCD is the most common cause of GN in individuals less than 20 year.The most common SGD in our study is Amyloidosis while in other studies & across the globe, has been documented as LN. Because of the heterogeneity among the findings of studies from different nephrology centers across India,it is necessary to maintain a central registry.

CONFLICT OF INTEREST: None declared

Ethics approval and consent to participate-All methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by a instituitional ethics committee of mahatma gandhi university of medical sciences and technology, jaipur. Informed consent was obtained from all subjects and/or their legal guardian(s).

• Consent for publication-not applicable

• Availability of data and materials-not applicable

• Competing interests-not applicable

• Funding-not applicable

• Authors' contributions-TV wrote the main manuscript text, collected data, made analysis, reviewed the data. NJ prepared tables and edited the manuscript. SG guided us regarding data collection and analysis. All authors reviewed the manuscript.

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No competing interests reported.

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A Clinicopathologic Study of Glomerular Disease: A Single-Center, Ten-year Retrospective Study from Northwest India

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