Clinicopathological correlation in lupus nephritis: a 5-year tertiary center experience using International Society of Nephrology/Renal Pathology Society classification

Abstract

Background and objective:

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predisposes individuals to multiple organ involvement, with renal complications, particularly lupus nephritis (LN), which is common and clinically significant. The classification and prognosis of LN largely depend on renal biopsy findings, including histopathology, direct immunofluorescence (IF), and electron microscopy. This study aimed to correlate clinicopathological features of SLE patients with LN classes according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification.

Methods:

This retrospective cohort study was conducted over 5 years and included 65 patients with biopsy-proven LN. Patients were categorized into six histological classes based on the ISN/RPS 2003 classification. Demographic, clinical, laboratory, histopathological, and IF data were collected and correlated. Statistical analysis was performed, and a P-value < 0.05 was considered significant.

Results:

Anemia was the most frequent hematological abnormality. Class IV LN was the predominant histologic subtype in 56.92% of the cases. Statistically significant associations were found between LN class and serum creatinine level, estimated glomerular filtration rate, proteinuria, and activity index. Interstitial fibrosis and tubular atrophy significantly correlated with elevated serum creatinine levels.

Conclusion:

This study highlights strong clinicopathological correlations in LN, especially between renal function parameters and histological indices. The integration of routine renal profiles, urine analysis, and histological scoring can guide clinical decision-making and underscore the utility of repeat biopsies during follow-up.

Introduction

Systemic lupus erythematosus (SLE) is a prototypical chronic autoimmune disease characterized by a broad spectrum of clinical manifestations, ranging from mild cutaneous symptoms to severe, life-threatening multiorgan involvement[1]. The clinical course of SLE is often unpredictable, with alternating periods of exacerbation and remission. Among the multiple organ systems affected, renal involvement, known as lupus nephritis (LN), remains one of the most common and serious complications, observed in 25–60% of patients^[2,3]. LN is a major predictor of morbidity and mortality in patients with SLE; if inadequately managed, it can potentially progress to end-stage renal disease (ESRD).

HIGHLIGHTS

• Class IV lupus nephritis was the most common subtype (56.9%) in the Indian cohort, thereby emphasizing its clinical predominance.

• Significant correlations were observed between International Society of Nephrology/Renal Pathology Society histological class and renal function parameters, including serum creatinine, estimated glomerular filtration rate, and proteinuria.

• Interstitial fibrosis and tubular atrophy were strongly associated with elevated serum creatinine levels, underscoring their prognostic relevance.

• Activity and chronicity indices correlated with both clinical markers and histological features, supporting their use in risk stratification.

The pathogenesis of SLE is multifactorial, and its progression remains incompletely understood. It involves a complex interplay between genetic, immunological, and environmental triggers. Microscopically, LN presents a range of glomerular, tubulointerstitial, and vascular findings, reflecting the heterogeneity of renal involvement in SLE[4]. However, these histopathological features do not always correlate well with clinical or laboratory findings, posing significant challenges for diagnosis and therapeutic decision-making.

In routine clinical practice, the management of LN depends on the careful integration of clinical, serological, and histopathological information to optimize treatment decisions and long-term outcomes. Although renal biopsy is the gold standard for diagnosis and classification, the extent to which biopsy-derived activity and chronicity indices mirror renal function, serological activity, and overall disease burden varies across different patient populations and care settings^[5,6]. Establishing robust clinicopathological correlations is therefore crucial to refine risk stratification, calibrate immunosuppressive intensity, and anticipate progression to chronic kidney disease (CKD) or ESRD[7].

Such correlations are particularly valuable for identifying patients who may benefit from early therapeutic escalation, closer clinical surveillance, or repeat renal biopsy in the setting of persistent proteinuria, declining estimated glomerular filtration rate (eGFR), or discordant clinical and serological findings. Against this background, the present study evaluates clinicopathological correlations among clinical, serological, and histopathological parameters at the time of renal biopsy in patients with biopsy-proven LN classified according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS).

Methods

This retrospective cohort study was conducted over 5 years at a single center. This study was conducted in accordance with the STROCSS criteria[8].

Patients were included in the study if they had a clinical and histological LN met by the American Rheumatology Association criteria for SLE, tested positive for antinuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) at any point during their disease course, and had an adequate renal biopsy specimen with more than six glomeruli[9].

The primary outcome of the study was the association between ISN/RPS histological class and renal function parameters, specifically serum creatinine levels and eGFR measured at the time of renal biopsy. The secondary outcomes included associations between histological activity and chronicity indices and relevant clinical, serological, and laboratory parameters, including proteinuria[10] and immunological markers.

All consecutive biopsy-proven cases of LN over the 5-year study period were included to maximize sample size. Given the retrospective nature of the study, no formal a priori sample size or power calculation was performed.

Demographic and laboratory data, including hypertension status, were obtained from medical records and the institutional registry. Patients were classified as hypertensive if a prior diagnosis of hypertension was documented in the registry. Serum creatinine values (mg/dL) were obtained using the modified Jaffe’s method. Twenty-four-hour urinary protein, complete blood count, ANA, and anti-dsDNA were noted at the time of biopsy. Microscopic hematuria was defined as the presence of more than five red blood cells per high-power field. Renal function was assessed using serum creatinine, and the eGFR was calculated using the Modification of Diet in Renal Disease equation[10]. GFR <60 mL/min/1.73 m² was indicated as CKD[11].

Ultrasound-guided renal biopsies were performed in all 65 patients using a semi-automated renal biopsy gun. The specimens were then processed using a standard light microscope. The sections were stained with hematoxylin and eosin, Periodic Acid–Schiff, Masson’s Trichrome, and Silver Methenamine for light microscopy. For Direct immunofluorescence (DIF), sections were incubated at 37°C for 1 hour with fluorescein isothiocyanate-conjugated antisera against human IgG, IgM, IgA, C3, and C1q (DAKO), diluted 1:40. Following three PBS washes, the sections were mounted using a glycerin-based medium and examined with a Nikon Eclipse 400 fluorescence microscope.

Two experienced renal pathologists independently reviewed all renal biopsy specimens. In cases of interpretative discordance, a joint review was conducted to achieve consensus on histological classification and scoring. All biopsies were classified according to the 2003 revised ISN/RPS classification system for LN by two experienced pathologists[12]. This system categorizes LN into six distinct classes based on glomerular involvement: Class I (minimal mesangial LN), Class II (mesangial proliferative LN), Class III (focal LN), Class IV (diffuse LN), which is further subclassified into segmental (Class IV-S) or global (Class IV-G), Class V (membranous LN), and Class VI (advanced sclerosing LN). DIF demonstrated findings based on location and intensity, categorized as 1+ to 3+.

Activity index (AI) and chronicity index (CI) were determined using the semiquantitative scoring system described by Austin et al[13]. CI quantifies the degree of irreversible renal damage in patients with LN. It is determined by summing the individual scores assigned to glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis, as outlined in the ISN/RPS classification. The CI ranges from 0 to 12, with higher scores indicating more advanced chronic pathological changes within the renal parenchyma[13]. Tubulointerstitial changes were assessed using a tubulointerstitial index (TI), scored as follows: a score of 0 for absence of interstitial fibrosis and tubular atrophy; 1+ when either lesion was present and graded >1+; and 2+ when both interstitial fibrosis and mononuclear infiltrates were present and graded >1+.

Statistical analysis

Data analysis was performed using GraphPad Prism. Continuous variables are presented as mean ± standard error, and categorical variables as frequencies and percentages. Group comparisons were conducted using the chi-square test or Fisher’s exact test for categorical variables and analysis of variance with post hoc testing for continuous variables, as appropriate. Associations were assessed using Spearman’s rank correlation. Multivariable linear regression analysis was performed with eGFR at the time of renal biopsy as the dependent variable, adjusting for age, sex, AI, and CI. Serum creatinine was excluded from the multivariable model because it is mathematically reliant on eGFR, thereby avoiding multicollinearity. Results are reported as β coefficients with 95% confidence intervals. A two-sided P value <0.05 was considered statistically significant.

Results

A total of 65 patients with biopsy-confirmed LN were included in the study. The patients’ ages ranged from 9 to 55 years, with a mean age of 30.12 years (±13.83). Most patients (41.54%, n = 27) were aged 21–30 years. The cohort demonstrated a pronounced female predominance, with 53 females (81.54%) and 12 males (18.46%), resulting in a female-to-male ratio of approximately 4.4:1.

Anemia was the most frequent hematological abnormality, observed in 59 of the 65 patients (90.77%). The overall clinical presentation of the patients is presented in Table 1. The baseline laboratory data at the time of renal biopsy are shown in Table 2.

Table 1.

Frequency of clinical presentations in patients with lupus nephritis

Symptoms	n (%)
Proteinuria	60 (92.3%)
Arthralgia	44 (67.6%)
Hypertension	40 (61.5%)
Edema	31 (47.6%)
Photosensitivity	12 (18.3%)
Rash	19 (29.2%)
Oral ulcer	24 (36.9%)
CNS symptoms	6 (9.2%)
Obstetrics (abortions)	7 (10.7%)

CNS, central nervous system.

Table 2.

Baseline demographic, clinical, and laboratory parameters at the time of renal biopsy in lupus nephritis patients

Parameters	Mean	STDEV
Age	30.12	13.83
Sex	1.82	0.39
Activity index	5.31	2.88
Chronicity index	2.97	2.46
Serum creatinine	1.73	1.07
eGFR	68.31	26.5
Blood urea	46.57	25.11
Hemoglobin	9.13	1.78
Proteinuria	2.14	0.73
Hematuria	1.17	0.45

eGFR, estimated glomerular filtration rate.

Renal biopsies were classified as I–VI according to the 2003 ISN/RPS classification system (Table 3). Class IV (diffuse LN) was the most common subtype, accounting for 37 of the 65 cases (56.92%). The detailed class-wise distribution of histopathological findings, including glomerular, tubulointerstitial, and vascular changes, is summarized in Table 4.

Table 3.

Distribution of LN classes based on ISN/RPS 2003 classification

Class	Frequency (%)
Class II	11 (16.92)
Class III	06 (9.23)
Class IV	37 (56.92)
Class V	08 (12.31)
Class VI	03 (4.62)

Class I: minimal mesangial LN; Class II, mesangial proliferative LN; Class III, focal LN; Class IV, diffuse LN; Class V, membranous LN; Class VI, advanced sclerosing LN; LN, lupus nephritis.

Table 4.

Class-wise distribution of histopathological features in LN based on ISN/RPS 2003 classification

Histopathology findings	Class I	Class II	Class III	Class IV	Class V	Class VI	P value
	n = 0	n = 11	n = 6	n = 37	n = 8	n = 3
	number (%)	number (%)	number (%)	number (%)	number (%)	number (%)
Mesangial hypercellularity	0	11 (100)	06 (100)	37 (100)	08 (100)	0
Leucocyte infiltration	0	0	04 (66.67)	33 (89.19)	01 (12.5)	1 (33.33)	<0.0001
Cellular crescents	0	0	0	13 (35.84)	0	0	0.0124
Glomerular sclerosis	0	2 (18.18)	02 (33.33)	14 (37.14)	04 (50)	3 (100)	0.1259
Interstitial fibrosis	0	2 (18.18)	02 (33.33)	22 (59.46)	05 (62.5)	3 (100)	<0.0001
Tubular atrophy	0	2 (18.18)	02 (33.33)	22 (59.46)	05 (62.5)	3 (100)	<0.0001

Class I not represented in biopsy cohort.

Class I, minimal mesangial LN; Class II, mesangial proliferative LN; Class III, focal LN; Class IV, diffuse LN; Class V, membranous LN; Class VI, advanced sclerosing LN; and LN, lupus nephritis.

Renal function, categorized by serum creatinine levels as normal to mild insufficiency (<1.5 mg/dL), moderate insufficiency (1.5–3.0 mg/dL), and severe insufficiency (≥3.0 mg/dL), did not differ significantly across ISN/RPS classes (P = 0.090; Table 5). However, when analyzed as a continuous variable, serum creatinine demonstrated a statistically significant association with ISN/RPS class. Hypertension was significantly associated with renal insufficiency (P = 0.0306) and with the histological class of LN according to the 2003 ISN/RPS classification system (P < 0.0001). Significant associations were found between LN class and proteinuria, serum creatinine, and eGFR. However, no significant associations were observed between LN class and hematuria, anemia, or blood urea nitrogen (BUN) levels. Notably, serum creatinine levels were significantly associated with both interstitial fibrosis (P = 0.0016) and tubulointerstitial inflammation (P < 0.0001).

Table 5.

Multivariable linear regression analysis of factors associated with estimated glomerular filtration rate (eGFR) at the time of renal biopsy (n = 65)

	β coefficient	Standard error	95% CI for β	P value
Intercept	102.34	17.92	66.55 to 138.13	<0.001
Age (per year)	−0.58	0.25	−1.07 to −0.09	0.021
Sex (male vs female)	−3.12	3.92	−9.45 to 3.21	0.329
Activity index	−0.41	0.40	−1.21 to 0.39	0.308
Chronicity index	−3.46	1.36	−6.19 to −0.74	0.014

The dependent variable was eGFR (mL/min/1.73 m²) measured at the time of renal biopsy. β coefficients represent the change in eGFR per unit increase in the predictor. Sex was entered as a binary variable (male = 1, female = 0; female as the reference category). Model fit statistics: R² = 0.41; adjusted R² = 0.36; overall model P < 0.001.

In a multivariable linear regression model adjusting for age, sex, AI, and CI (Table 6), a higher CI was independently associated with lower eGFR at the time of renal biopsy (β = −3.46 per one-point increase; 95% CI −6.19 to −0.74; P = 0.014). Increasing age was also independently associated with lower eGFR (β = −0.58 per year; 95% CI −1.07 to −0.09; P = 0.021). In contrast, sex and AI were not independently associated with eGFR after adjustment.

Table 6.

Distribution of renal insufficiency grades across LN patients on serum creatinine levels

Sr. Creatinine	Class II	Class III	Class IV	Class V	Class VI	P value
	N (%)	N (%)	N (%)	N (%)	N (%)
Mild (<1.5)	10 (90.91)	05 (83.33)	19 (51.35)	2 (25)	0	0.090
Moderate (1.5–3)	01 (09.09)	01 (16.67)	16 (43.24)	5 (62.5)	1 (33.33)
Severe >3	0	0	2 (05.4)	1 (12.5)	2 (66.67)

Sr.Creatinine, Serum Creatinine; Class I, minimal mesangial LN; Class II, mesangial proliferative LN; Class III, focal LN; Class IV, diffuse LN; Class V, membranous LN; Class VI, advanced sclerosing LN; and LN, lupus nephritis.

Of the 65 patients, 23 (35.38%) had an eGFR <60 mL/min/1.73 m², and two (3.08%) had an eGFR <15 mL/min/1.73 m². The highest mean eGFR was observed in Class II LN, and the lowest in Class VI. A statistically significant correlation was identified between LN class and eGFR (P = 0.0381), indicating a decline in renal function with an advancing histopathological class (Table 7).

Table 7.

Class-wise comparison of clinicopathological parameters in LN patients

	II	III	IV	V	VI	P value
	Mean (SD)	Mean (SD)	Mean (SD)	Mean (SD)	Mean (SD)
Age	36.18 (±16.93)	27.4 (±11.25)	27.57 (±12.42)	35.75 (±12.53)	36.33 (±7.13)	0.1756
Hb	9.64 (±1.61)	9.80 (±0.98)	9.01 (±1.84)	9.50 (±1.41)	7.33 (±1.89)	0.3533
Activity index	2.27 (±1.14)	7.17 (±2.478)	6.14 (±2.54)	6.00 (±2.00)	0.67 (±0.94)	<0.0001
Chronicity index	0.36 (±0.77)	2.00 (±1.41)	3.49 (±1.98)	3.25 (±2.77)	7.67 (±1.70)	<0.0001
Tubulointerstitial index	1.27 ± 2.452	2 ± 1.732	3.43 ± 2.455	4.13 ± 3.257	8	0.0018
Serum creatinine	1.11 (±0.55)	1.22 (±0.29)	1.81 (±1.12)	1.89 (±0.58)	3.7 (±0.99)	0.0021
Blood urea	34.8 (±13.29)	37.67 (±9.88)	49.358 (±28.19)	45.880 (±10.96)	53.330 (±10.28)	0.34
Proteinuria	0.73 (±0.37)	1.110 (±0.31)	2.42 (±1.20)	2.18 (±0.69)	2.92 (±1.19)	<0.0001
Hematuria	1.18	1.20	1.16	1.25	1.00	0.956
eGFR	87 (±16.64)	74.17 (±12.35)	65.3 (±26.63)	62.63 (±30.02)	40.33 (±20.17)	0.0381.

Hb, hemoglobin; eGFR, estimated glomerular filtration rate; Class I, minimal mesangial LN; Class II, mesangial proliferative LN; Class III, focal LN; Class IV, diffuse LN; Class V, membranous LN; Class VI, advanced sclerosing LN; and LN, lupus nephritis.

ANA results were available for all 65 patients, of whom 62 (95.38%) tested positive. Anti-dsDNA antibodies were detected in 57 of the 65 patients (87.69%). Immunofluorescence (IF) staining revealed full-house positivity for immunoglobulins IgG, IgA, IgM, and complement C3c and C1q in 48 patients (73.85%). The remaining 17 (26.16%) patients did not exhibit full-house staining.

Discussion

Renal involvement is a common and severe manifestation of SLE, often influencing both morbidity and prognosis[14]. Accurate identification and classification of glomerular pathology in LN remain critical yet complex tasks in renal pathology. After multiple revisions, the 2003 ISN/RPS classification system gained widespread acceptance for its standardized histopathologic framework for evaluating LN.

In this study, a marked female predominance was observed, consistent with previous literature^[15,16]. The higher susceptibility of females to LN may be attributed to hormonal influences, specifically the pro-inflammatory role of estrogens and the absence of protective androgens. This concept is supported by murine models, such as those of Koffler et al, where estrogen administration or androgen deprivation precipitated lupus-like disease^[17,18].

Clinical presentations in our cohort were largely consistent with previously published reports; however, neurological manifestations were less frequently documented, which may reflect underrecognition or underreporting of subtle symptoms such as headaches or mood disturbances^[16,19–21]. Hypertension was observed in 61.5% of patients at the time of diagnosis, reflecting its known association with disease severity and renal impairment.

Proteinuria was the most frequent presenting feature in 60 patients (92.3%), followed by arthralgia in 44 patients (67.6%), and edema in 47 patients (67.6%). These findings are consistent with those reported by Satish et al and Leaker et al^[22,23]. Notably, proteinuria, a hallmark of LN, was associated with ISN/RPS LN classes, with Class IV patients more frequently presenting with nephrotic-range proteinuria. Although nephrotic syndrome has traditionally been linked to Class V LN^[16,24], in our study, only three of eight patients with Class V disease exhibited nephrotic syndrome. This aligns with the findings of Satish et al and could be attributed to the small number of Class V cases in our cohort[21].

Anemia was notably more prevalent in our population compared to other reported cohorts, with 18.1% of patients having hematocrit levels below 24%^[20,25]. Austin et al identified hematocrit <20% as a poor prognostic factor[13]. The mean BUN and serum creatinine levels in our study were consistent with those reported by Seedat et al[26] and others^[27–29].

Significant correlations were noted between LN class and both serum creatinine and eGFR, with the lowest renal function observed in Class IV. These findings are consistent with those of earlier studies[16], including those by Austin et al, who highlighted elevated serum creatinine at the time of biopsy as a strong predictor of renal failure[13]. Furthermore, serum creatinine showed statistically significant correlations with histological features, including tubular atrophy, interstitial fibrosis, and tubulointerstitial inflammation (P < 0.0001). The TI index reflects tubulointerstitial injury, increasingly recognized as a key determinant of renal prognosis in LN, often showing a stronger correlation with decline in glomerular filtration rate than glomerular lesions alone. These results corroborate those of previous reports by Hill et al and others, who identified interstitial inflammation as a critical predictor of renal dysfunction^[30,31].

The mean activity was 5.31 ± 2.88, and the CI was 2.97 ± 2.46. Higher chronicity scores are commonly associated with persistent proteinuria, which may contribute to ongoing tubulointerstitial injury, a recognized pathway in the progression of ESRD. Therefore, early renal biopsy is essential for guiding therapeutic decisions and preventing irreversible damage.

In this study, we found significant correlations between AI and key clinical parameters, including 24-hour urinary protein, blood urea, and serum creatinine, all of which were statistically significant (P < 0.001). Further analysis revealed a positive association between urinary protein levels and histological activity, reinforcing proteinuria’s role as a marker of active renal inflammation. Notably, the highest activity scores were recorded in patients classified as having Class III and Class IV LN, reflecting the more aggressive disease phenotype typically observed in these subclasses.

We observed a significant association between elevated serum creatinine and chronic histologic features, including glomerulosclerosis and tubulointerstitial fibrosis (P = 0.0003), thereby reinforcing the prognostic significance of these features. The presence of both chronic interstitial changes and active lesions, particularly cellular crescents, has been associated with adverse outcomes, including progression to ESRD. Our findings were consistent with those reported by Nivedita et al[32].

Although anti-dsDNA antibodies were negative in eight patients, ANA positivity was observed in all cases, underscoring the high sensitivity of ANA testing for the diagnosis of lupus. These findings are consistent with those reported by Nivedita J[32], supporting the role of serological markers in reflecting renal disease activity in LN. Interestingly, two cases of Class II LN lacked immune deposits on IF, raising the possibility of lupus podocytopathy, a distinct entity typically diagnosed by electron microscopy. Among the immunoglobulins and complement components detected by IF, IgG was the most frequently observed (87.69%), followed by C1q (76.92%) and C3c (60%), consistent with the deposition patterns reported in previous studies, including that by Venishetty et al[33].

This study has certain limitations inherent to its retrospective design. The analysis primarily reflects clinical, serological, and histopathological parameters assessed at the time of renal biopsy, and long-term follow-up data regarding renal survival, progression to CKD or ESRD, and response to therapy were not consistently available for all patients due to referral patterns and loss to follow-up. In addition, although multivariable analyses were performed to adjust for key confounders, the modest sample size precluded including additional covariates. Furthermore, while all renal biopsies were independently reviewed by two experienced renal pathologists with consensus resolution of discrepancies, formal assessment of interobserver variability using statistical measures such as kappa coefficients was not performed, representing a methodological limitation.

Nevertheless, the clinicopathological correlations observed at baseline remain clinically meaningful, as histological activity and chronicity indices at the time of biopsy are well-established predictors of long-term renal outcomes in LN. Future multi-institutional studies with larger cohorts and standardized longitudinal follow-up are warranted to validate and extend these findings.

Conclusion

Our study demonstrated significant clinicopathological correlations in LN, particularly between renal function parameters and histological activity, chronicity, and tubulointerstitial indices as defined by the ISN/RPS classification. Our findings highlight the importance of integrating clinical, serological, and detailed histopathological assessment at the time of renal biopsy to improve risk stratification and guide individualized therapeutic decision-making. The strong associations between chronic histological changes and impaired renal function underscore the value of activity and chronicity indices in identifying patients at higher risk of adverse renal outcomes and in informing the intensity of immunosuppressive therapy. In addition, these results support the selective use of repeat renal biopsy in patients with discordant clinical and histological features or persistent disease activity.

Biography

Shree L.D. Singaravelu and Saima Ejaz are contributed equally.

Ethical approval

All methods in this retrospective study were conducted in accordance with the ethical standards of the institutional research committee and the principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the Institutional Ethics Committee of Kasturba Medical College, Manipal, on 10 September 2011, prior to data collection.

Consent

As this was a retrospective analysis of anonymized medical records and renal biopsy specimens, the Ethics Committee waived the requirement for written informed consent. Patient confidentiality was strictly maintained, and no identifiable personal information was included in the analysis or manuscript.

Sources of funding

The authors received no specific funding for this work.

Author contributions

B.R. and L.R. participated in the conception and design of the study and were involved in the acquisition, analysis, and interpretation of data. A.S.C. wrote the manuscript. S.L.D.S. and B.R. accessed and verified the study data. All authors critically reviewed and provided final approval of the manuscript; all authors were responsible for the decision to submit the manuscript for publication.

Conflicts of interest disclosure

The authors declare no conflicts of interest, financial, or otherwise, that could have influenced the research.

Research registration unique identifying number (UIN)

This study was not registered in a public clinical trial registry because it was a retrospective observational analysis using anonymized clinical and histopathological data and did not involve any prospective intervention or participant enrollment.

Guarantor

Brahmaiahchari Rangachari.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statement

Data available on request from the authors.

Acknowledgements

The authors would like to express their gratitude to Department of Pathology, Kasturba Medical College, Manipal, India, for providing the facilities necessary to conduct this study. The first authior would like to sincerely acknowledge Dr. Prabhu, Department of Nephrology, Kasturba Medical College, for his continued support and for facilitating access to samples and clinical data essential for this study.