Landscape of kidney biopsy diagnoses in a Romanian pediatric cohort

Abstract

Background

There is relatively little information available on the landscape of histological findings in kidney biopsies of pediatric populations, particularly in Eastern Europe.

Methods

Records of pediatric native kidney biopsies processed between 1996 and 2023 were extracted from the registry of the Victor Babeş National Institute of Pathology, Bucharest. Demographic characteristics, biopsy indications and histopathological findings, as well as temporal trends thereof, were analyzed and compared to those reported in other European studies.

Results

A total of 326 native pediatric kidney biopsy records were identified. The most common biopsy indications were urinary abnormalities (32.8%) and nephrotic syndrome (30.4%). A clinical systemic lupus erythematosus (SLE) diagnosis constituted the main biopsy indication in 17.8% of cases, among which we identified 17 patients with no overt renal involvement, in whom kidney lesions were nonetheless found upon biopsy for all but one. The most frequent histopathological diagnoses overall were: lupus nephritis (LN; 17.8%), minimal change disease (MCD; 16.3%), IgA nephropathy (including IgA vasculitis; 14.1%), Alport syndrome/thin basement membrane disease (Alport/TBMD; 11.3%) and focal segmental glomerulosclerosis (6.7%). LN and MCD frequencies increased over time, while Alport/TBMD frequencies decreased.

Conclusions

This study addresses an important gap in the landscape of pediatric biopsy-proven kidney diseases in Europe. While our results largely mirror those reported in other European studies, one important difference lies in the high proportion and increasing trend of LN cases, driven by shifts in local practices towards more accurate assessment of SLE patients, to obtain histopathological evaluation and classification of LN in its earliest stages.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12882-026-04994-y.

Background

The causes of chronic kidney disease (CKD) in the pediatric population exhibit a number of important differences to the adult population, and, in comparison, remain largely undercharacterized. While data on pediatric patients receiving kidney replacement therapy (KRT) are available in most European countries, data on earlier stages of CKD are considerably scarcer [1]. As a consequence, the prevalence and etiologies of CKD in this population are poorly understood, and current estimates of CKD burden are believed to be underestimated [2]. The most common causes of CKD in children are congenital anomalies of the kidney and urinary tract, and hereditary nephropathies – estimated to account for two thirds of all cases of CKD in developed countries [1]. Since the advent of kidney failure at a young age constitutes a long-term health issue, an improved understanding of the landscape of kidney diseases and the associated histopathological lesions, is paramount. Kidney biopsy remains the gold standard in diagnosing and grading kidney disease, with histopathological characterization contributing crucially to treatment optimization, as well as providing insights into progression risk factors.

In this study, we report on the demographic characteristics, biopsy indications and histopathological findings in a Romanian pediatric cohort, consisting of subjects younger than 18 years, who underwent kidney biopsy between 1996 and 2023. We also report on changes observed in these variables over time. Where available, information on repeated biopsies are also presented.

Methods

Data sources

Pediatric kidney biopsy records were extracted from the registry of the Victor Babeş National Institute of Pathology. Transplant biopsies were excluded. In cases of repeated biopsies, where the first biopsy was inconclusive due to inadequate material, only the second biopsy was retained in the analysis. After identifying patients who underwent kidney biopsy procedures as children, the registry was queried to identify follow-up biopsies, including those potentially performed at adult-age. This retrospective study was approved by the Ethics Committee of the Victor Babeș National Institute of Pathology (nr. 120/06.02.2024).

Biopsy indications and histopathological evaluation

The main referral centre for biopsies evaluated at our center is the Fundeni Clinical Institute, but our center occasionally receives kidney biopsies from other major pediatric hospitals in Bucharest, and sporadically from other counties. Biopsy indications include nephrotic syndrome (NS; defined according to guidelines in place at the time of biopsy as heavy proteinuria, hypoalbuminemia, hyperlipidemia and edema; this category also includes steroid-dependent, steroid-resistant, and relapsing NS), urinary abnormalities (UA; defined as isolated proteinuria, isolated hematuria, or combined proteinuria and hematuria), a clinical diagnosis of systemic lupus erythematosus (SLE), chronic kidney disease (CKD) and acute kidney injury (AKI).

Biopsy specimens were evaluated under light, immunofluorescence and electron microscopy. Electron microscopy (EM) is routinely performed, unless the biopsy material is inadequate. All biopsies were evaluated by one of four nephropathologists. Diagnosis categories follow the classification proposed by Laurens et al. [3] Where necessary, diagnosis records were reviewed, and classified into one of these categories.

Statistical analysis

Categorical variables are presented as counts and percentages, and continuous variables are summarised by their median values and corresponding inter-quartile ranges (IQR). Differences in distribution of categorical or continuous variables among groups were evaluated using Chi-squared or Mann-Whitney tests, respectively. Age groups were defined based on the intervals 0–8, 9–12, 13–15 and 16–17 years; these intervals were chosen based on age quartiles in the cohort, to obtain a relatively equal distribution of subjects among groups. Time trends were evaluated by splitting the study period into four 7-year intervals (1996–2002, 2003–2009, 2010–2016, 2017–2023), as well as by using linear or logistic regression against the year of the biopsy, and including adjustment for age (as a continuous variable) and sex; we report conditional odds ratios (cOR), together with 95% confidence intervals (95%CI) and corresponding p-values. For a given diagnosis, these analyses model the probability of receiving that diagnosis, given age, sex and year of biopsy. A positive coefficient of the year of biopsy indicates an increasing temporal trend, and conversely, a negative coefficient indicates a decreasing temporal trend. The quadratic contribution of the year of biopsy was also evaluated, in order to explore possibly nonlinear temporal trends. The detailed results of all regression analyses can be found in Table S1 of the Supplementary material.

All p-values reported are two-sided, with 0.05 taken as the significance threshold. All statistical analysis were carried out using R (v4.4.1) in RStudio (v2024.9.1).

Results

Cohort description

A total of 336 pediatric kidney biopsy records were identified in our registry. Of these, 4 transplant biopsies, and 6 biopsies of inadequate quality, which were repeated, were excluded. This resulted in 326 pediatric biopsies retained for analysis. In 16 patients, a second biopsy was identified: 14 patients repeated the biopsy while still under the age of 18, and 2 repeated the biopsy at adulthood.

Biopsies of male patients represented 53.1% and saw a small, non-significant decline over the study period, from 61.1% in 1996–2002, 54.1% in 2003–2009 and 54.3% in 2010–2016, to 49.7% in 2017–2023. Age at biopsy did not differ significantly between male and female patients (p = 0.103), and registered a mild, non-significant, decrease between the periods 1996–2002 (median: 15.0, IQR: 10.0–16.0), 2010–2016 (median: 11.0, IQR: 7.5–16.0), and 2010–2016 (median: 12.0, IQR: 8.3–14.8), followed by a compensatory increase in the period 2017–2023 (median: 14.0, IQR: 10.6–16.0, p = 0.024). This was supported by significant negative linear and positive quadratic contributions of the year of biopsy in linear regression. However, this trend was mainly driven by the male subcohort; age at biopsy in the female subcohort remained relatively stable throughout the study period (Table 1).

Table 1.

Cohort demographic characteristics, biopsy indications and histopathological diagnoses

Variable	Overall (n = 326)	1996–2002 (n = 54)	2003–2009 (n = 61)	2010–2016 (n = 46)	2017–2023 (n = 165)
Sex
Male	173 (53.1%)	33 (61.1%)	33 (54.1%)	25 (54.3%)	82 (49.7%)
Female	151 (46.3%)	20 (37%)	27 (44.3%)	21 (45.7%)	83 (50.3%)
Unknown	2 (0.6%)	1 (1.9%)	1 (1.6%)	-	-
Age (years)
Age entire cohort	13 (9.0–16.0)	15 (10–16)	11 (7.5–16)	12 (8.3–14.8)	14 (10.6–16.0)
Age male patients	13 (9.0–16.0)	15 (10.5–16)	11 (7.5–14.75)	9 (7.5–12)	14 (11–16)
Age female patients	14 (10.0–16.0)	11.5 (9.5–17)	12 (9.5–16)	14 (12.5–15.5)	14 (10.2–16)
Biopsy indication
UA	107 (32.8%)	21 (38.9%)	19 (31.1%)	12 (26.1%)	55 (33.3%)
NS	99 (30.4%)	20 (37%)	20 (32.8%)	17 (37.0%)	42 (25.5%)
SLE	58 (17.8%)	3 (5.6%)	5 (8.2%)	9 (19.6%)	41 (24.8%)
CKD	26 (8.0%)	3 (5.6%)	10 (16.4%)	4 (8.7%)	9 (5.5%)
AKI	30 (9.2%)	7 (13%)	6 (9.8%)	2 (4.3%)	15 (9.1%)
Unknown	6 (1.8%)	0 (0%)	1 (1.6%)	2 (4.3%)	3 (1.8%)
Histopathological diagnosis *
Lupus nephritis	58 (17.8%)	2 (3.7%)	8 (13.1%)	11 (23.9%)	37 (22.4%)
MCD	53 (16.3%)	6 (11.1%)	7 (11.5%)	7 (15.2%)	33 (20.0%)
IgA nephropathy	46 (14.1%)	6 (11.1%)	11 (18.0%)	6 (13.0%)	23 (13.9%)
Alport/TBMD	37 (11.3%)	15 (27.8%)	9 (14.8%)	3 (6.5%)	10 (6.1%)
FSGS	22 (6.7%)	3 (5.6%)	2 (3.3%)	2 (4.3%)	15 (9.1%)
Normal kidney histology	14 (4.3%)	1 (1.9%)	4 (6.6%)	4 (8.7%)	5 (3.0%)
Membranous nephropathy	11 (3.4%)	4 (7.4%)	1 (1.6%)	2 (4.3%)	4 (2.4%)
Infection-related immune-complex GN	10 (3.1%)	4 (7.4%)	4 (6.6%)	1 (2.2%)	1 (0.6%)
Tubulointerstitial nephritis	9 (2.8%)	2 (3.7%)	-	1 (2.2%)	6 (3.6%)
C3 glomerulopathy	8 (2.5%)	4 (7.4%)	1 (1.6%)	-	3 (1.8%)
No diagnosis**	7 (2.1%)	-	2 (3.3%)	1 (2.2%)	4 (2.4%)
Thrombotic microangiopathy	7 (2.1%)	-	2 (3.3%)	2 (4.3%)	3 (1.8%)
AAV	5 (1.5%)	-	-	-	5 (3%)
Global glomerulosclerosis	3 (0.9%)	-	-	1 (2.2%)	2 (1.2%)
IgM nephropathy	3 (0.9%)	-	1 (1.6%)	2 (4.3%)	-
Medication-induced nephropathy	3 (0.9%)	-	-	-	3 (1.8%)
Amyloidosis	2 (0.6%)	1 (1.9%)	1 (1.6%)	-	-
Anti-GBM nephritis	2 (0.6%)	-	1 (1.6%)	-	1 (0.6%)
Cystic kidney disease	2 (0.6%)	-	-	-	2 (1.2%)
End-stage kidney disease	1 (0.3%)	-	-	-	1 (0.6%)
Fabry	1 (0.3%)	-	-	-	1 (0.6%)
Lymphoma	1 (0.3%)	-	-	1 (2.2%)	-
Nephrocalcinosis	1 (0.3%)	-	-	1 (2.2%)	-
Nephrosclerosis	1 (0.3%)	-	-	-	1 (0.6%)

*The biopsy material was inadequate for histopathological evaluation in 19 (5.8%) cases

**No diagnosis: histological findings were inconclusive

UA: urinary abnormalities; NS: nephrotic syndrome; SLE: Systemic lupus erythematosus; CKD: chronic kidney disease; AKI: acute kidney injury; AAV: ANCA-associated vasculitis and pauci-immune glomerulonephritis; MCD: Minimal change disease; FSGS: Focal segmental glomerulosclerosis; TBMD: Thin basement membrane disease

The most frequent biopsy indications were UA and NS, at 32.8% (n = 107) and 30.4% (n = 99), respectively. A further 9.2% (n = 30) had AKI, and 8.0% (n = 26) had CKD. A SLE diagnosis was the main biopsy indication in 17.8% (n = 58) cases. In 1.8% (n = 6) of cases, the biopsy indication was unavailable in the records. With the exception of SLE, which saw consistent increases across time, from 5.6% (n = 3) in 1996–2002, to 8.2% (n = 5) in 2003–2009, 19.6% (n = 9) in 2010–2016, and 24.8% (n = 41) in 2017–2023, other biopsy indication frequencies remained relatively stable across time. With a median age of 16.0 years (IQR:14.0–17.0 years), patients with SLE were significantly older than those with other biopsy indications (p < 0.001), and were more likely to be female (22.4% male vs. 77.6% female, p < 0.001). Conversely, patients with NS were significantly younger than those with other biopsy indications (median age: 11 years, IQR: 6.0–15.0 years, p < 0.001), and patients with UA were more likely to be male (73.8% male vs. 26.2% female, p < 0.001).

Table 1 and Fig. 1 contain more detailed representations of age and sex distributions across the 7-year intervals, and across biopsy indications.

Fig. 1.

Age and sex distributions. (a) Age distribution among sexes; (b) Sex distribution across 7-year intervals; (c) Age distributions per sex across 7-year intervals; (d) Sex distribution across biopsy indication categories; (e) Age distribution across biopsy indication categories. ***: p-value < 0.001; **: 0.001 ≤ p-value < 0.01; *: 0.01 ≤ p-value < 0.05

Histopathological diagnoses

The most common diagnoses were lupus nephritis (LN; 17.8%, n = 58), minimal change disease (MCD; 16.3% n = 53), followed closely by IgA nephropathy (IgAN; 14.1%, n = 46), Alport or thin basement membrane disease (Alport/TBMD; 11.3%, n = 37) and focal segmental glomerulosclerosis (FSGS; 6.7%, n = 22). Among cases with a diagnosis of IgA nephropathy, 15 (32.6%) had presented with Henoch-Schönlein purpura. In 19 cases (5.8%), the material was inadequate for analysis. Of the 307 biopsies where adequate material was available for histopathological evaluation, EM was performed in 99.0% (n = 304) of the cases (in 3 cases, there was insufficient material for this modality).

Trends in histopathological diagnoses

LN showed a steady increase from 3.7% (n = 2) of biopsies processed in 1996–2002, to 13.1% (n = 8) in 2003–2009 and 23.9% (n = 11) in 2010–2016, and then decreased slightly to 22.4% (n = 37) in 2017–2023; this was mirrored by a significant positive contribution of the year of biopsy in the logistic regression model adjusting for age and sex (cOR 1.06, 95%CI: 1.02–1.10, p = 0.009). MCD frequencies registered an increase across study periods, from 11.1% (n = 6) in 1996–2002, and 11.5% (n = 7) in 2003–2009, to 15.2% (n = 7) in 2010–2016, and 20.0% (n = 33) in 2017–2023; this was reflected in a significant positive coefficient of the year of biopsy when adjusting for age and sex in logistic regression (cOR 1.04, 95%CI: 1.004–1.09, p = 0.035). Alport/TBMD frequencies registered a decrease across study periods, from 27.8% (n = 15) in 1996–2002, to 14.8% (n = 9) in 2003–2009, 6.5% (n = 3) in 2010–2016 and 6.1% (n = 10) in 2017–2023. This was mirrored by significant negative coefficients of the year of biopsy in the logistic models fitted (cOR: 0.93, 95%CI: 0.89–0.97, p = 0.001). Frequencies of IgAN and FSGS did not register any significant changes across the four 7-year intervals.

Diagnosis frequencies for each 7-year time period are depicted in Fig. 2. Detailed regression results for all models fitted can be found in Table S1 of the Supplementary material.

Fig. 2.

Frequencies of main diagnoses over time. TBMD: thin basement membrane disease; FSGS: focal segmental glomerulosclerosis; IgAN: IgA nephropathy; MCD: minimal change disease

Association between histological findings and sex

The most frequent diagnosis among male subjects was IgAN (19.7%, n = 34) followed by MCD (18.5%, n = 32) and Alport/TBMD (13.9%, n = 24). Among female subjects, the most frequent diagnosis was LN (28.5%, n = 43), followed by MCD (13.2%, n = 20), and Alport/TBMD (8.6%, n = 13). Significant differences in sex distribution were found among LN and membranous nephropathy (MN) subjects, which were dominated by female subjects (LN: 74.1% female, p < 0.001; MN: 81.8% female, p = 0.035), while subjects with IgAN were predominantly male (IgAN: 73.9% males, p = 0.001).

Association between histological findings and age

The most common diagnosis among patients in the 0–8 year age group was MCD (25.8%, n = 17). In the 9–12 year age group, the most common diagnoses were MCD and IgAN, at 17.3% (n = 13) each. In both the 13–15 and 16–18 year age groups, the most common diagnosis was LN, at 25.6% (n = 21) and 28.0% (n = 26), respectively. For comparison, the percentage of LN in among patients in the 0–8 and 9–12 year age groups were 3.0% and 9.3%, respectively.

Association between histological findings and biopsy indication

Among patients with UA and NS as a biopsy indication, the most common diagnoses were IgAN and MCD, at 37.4% and 41.4%, respectively. SLE subjects received a confirmatory LN primary diagnosis in 86.2% cases. Subjects with CKD and AKI exhibited higher diversity of histopathological diagnoses. Conversely, 87.7% of subjects with LN had a clinical SLE diagnosis. The most common indications among subjects diagnosed with IgAN and Alport/TBMD were UA, at 87.0% and 75.7%, respectively. NS was the most common indication among subjects diagnosed with FSGS and MCD, at 66.7% and 80.4%, respectively.

The frequencies of the most common diagnoses across sexes, age groups and biopsy indications, and conversely, the distribution of sex, age and biopsy indications across main histological diagnoses are depicted in Figs. 3 and 4, respectively.

Fig. 3.

Frequencies of main diagnoses among (a) sexes, (b) age groups, and (c) biopsy indications. F: female; M: male; UA: urinary abnormalities; NS: nephrotic syndrome; SLE: Systemic lupus erythematosus; CKD: chronic kidney disease; AKI: acute kidney injury; TBMD: thin basement membrane disease; FSGS: focal segmental glomerulosclerosis; IgAN: IgA nephropathy; MCD: minimal change disease

Fig. 4.

Distribution of (a) sex, (b) age, and (c) biopsy indications, among the main histological diagnoses. F: female; M: male; UA: urinary abnormalities; NS: nephrotic syndrome; SLE: Systemic lupus erythematosus; CKD: chronic kidney disease; AKI: acute kidney injury; TBMD: thin basement membrane disease; FSGS: focal segmental glomerulosclerosis; IgAN: IgA nephropathy; MCD: minimal change disease

Biopsy findings in patients with SLE without overt kidney involvement

Among patients with SLE as the main biopsy indication, 17 (29.3%) had no overt kidney involvement. Nonetheless, upon biopsy, 10 (58.8%) were diagnosed with Class I LN, 3 (17.6%) with Class II LN, 2 (11.8%) with Class III LN, and one (5.9%) with Class IV LN. In one patient (5.9%), no kidney lesions were found.

Repeated biopsies

Of the patients included in the analysis, 14 underwent a second biopsy procedure before the age of 18 years, and 2 after the age of 18 years. LN was the initial diagnosis in 7 patients, and 4 of these were assigned a lower class at the second biopsy. Two subjects initially diagnosed with MCD transitioned to FSGS; a third patient initially diagnosed with MCD was diagnosed with thrombotic microangiopathy at the second biopsy. One subject, initially diagnosed with nephrocalcinosis, experienced kidney failure. Biopsy indications and diagnoses received at repeat biopsies are presented in Table S2 of the Supplementary material.

Discussion

Our study adds to the scarce literature describing kidney biopsy findings in pediatric populations in Europe. To our knowledge, this is the first registry-based study reporting on histopathological findings in kidney biopsies of pediatric patients in Romania, and one of only a few Eastern European reports, especially in recent periods. An overview of similar published European reports is presented in Table S3 of the Supplementary material. With the exception of Spain, Norway, Italy and the Czech Republic, who have well established nationwide renal biopsy registries from which adult population studies are also available in the literature, reports mainly come from single-center or regional registries. Cohort sizes are modest in most cases, ranging between 148 and 575 subjects; the largest cohorts come from the Spanish national biopsy registry, which accrued 1231 pediatric patients over 26 years [4], and the national kidney biopsy registry of the Czech Republic [5], which reports 710 pediatric biopsies; the smallest cohorts, of 65 and 54 patients, respectively, originate from two single center studies in Croatia [6, 7]. Although interpretation of differences between reports is challenging, due to differing study periods covered, and associated changes in practices over time, different referral and biopsy indication protocols across centers and countries, use of EM as a diagnostic modality, as well as genetic or demographic characteristics of the underlying populations, some general trends can be identified. In particular, male patients most often represent the majority of subjects included in the study, and the median age is often approximately 10 years. IgAN (including Henoch-Schönlein purpura) and MCD are consistently reported as the most frequent diagnoses, while the proportion of patients diagnosed with LN varies between 1.5% and 15.0%. TBMD and Alport syndrome frequencies are generally very low, particularly in studies reporting irregular or infrequent use of EM as diagnostic modality. It should be noted that routine EM examination is reported in only 2 of the studies included in this comparison, both from the same single center in Croatia [6, 7]. FSGS frequencies are relatively consistent across studies.

In our cohort, we identified male predominance, at 53.1%, which saw no significant change over time. Our pediatric population was slightly older than those of other studies, with a median age of 13.0 years. MCD and IgAN were among the most frequent diagnoses, at 16.3% and 14.1%, respectively, but the most frequent diagnosis in our cohort was LN, at 17.8%. This is consistent with the slightly higher age of our cohort, since these patients are often referred for a renal biopsy with a clinical diagnosis of SLE, for which an onset during puberty is typical [8]. TBMD/Alport frequency was high, compared to other published reports, at 11.3%, likely due to the fact that these diagnoses require EM examination [9], which is routinely performed at our center. FSGS frequency was 6.7% in our study, which is consistent with findings of other studies. Our study also confirms the predominance of females among LN patients, and the predominance of males among IgAN patients, consistent with literature reports from adult and pediatric populations alike. For young patients (0–12 years), MCD was the most frequent diagnosis, but was replaced by LN in the range 13–18 years.

Temporal trend reports in diagnosis frequencies seem contradictory between published studies, and are rarely supported by statistical quantification. In our study, we found a decrease in Alport/TBMD frequencies, and an increase in MCD frequencies over time, which seemed to stabilize over more recent periods. The former can be attributed to the fact that a high-confidence TBMD diagnosis can generally be made based on clinical features and family history for typical presentations, together with the shift to genetic testing as the diagnostic gold standard in cases where a suspicion of Alport syndrome exists. The latter likely reflects a changing attitude towards biopsy in children presenting with NS, favouring early histopathological confirmation, enabled by the standard use of EM in the diagnostic workflow within our center, which allows identification of foot process effacement in its earliest stages.

Most notably, however, we identified an increasing trend in LN diagnoses, which was also reflected in the adult population of our registry [10]. This, together with the observed increase in SLE as the main biopsy indication reflects a change in referral patterns and biopsy practices. The decision to perform a kidney biopsy in patients with SLE was based on the treating nephrologist’s assessment of potential kidney involvement. While classical indications such as proteinuria, hematuria, or declining kidney function were part of this assessment, increasing attention was also given to the possibility of subclinical (“silent”) LN, and a more proactive biopsy strategy was adopted in these patients in the last decade. This shift is consistent with increasing awareness of the severity of childhood-onset LN, and the growing body of evidence suggesting that clinical presentation in these patients may not reveal the full extent of renal involvement [11, 12]. In particular, patients with SLE, normal kidney function and low-grade proteinuria may still have substantial kidney injury when biopsied. Our study confirms this: of the 17 patients with a clinical diagnosis of SLE and no overt kidney involvement who underwent kidney biopsy, only one patient was found to have no lesions. Reported associations between the initial biopsy class and the maintenance of stable remission [13], as well as the probability of relapse [8], suggest that early identification of kidney involvement may improve outcomes for these patients. Similarly, discordance between clinical and histological remission [14], support the value of repeat biopsies for decisions around maintenance therapy. We identified 7 LN patients with repeat biopsies, 2 of whom repeated the biopsy as adults (≥ 18 years), and 4 of whom were assigned a lower class at the second biopsy. An increasing LN diagnosis frequency was also reported in Sousa et al. (2024) [15], while Coppo et al. (1998) [16] reported a decreasing trend. As previously mentioned, comparisons between studies are complicated by the difference in time-intervals covered, given the associated changes in biopsy practices across time; this may provide a reasonable explanation for the contradictory data in this case, since the latter study covered the period 1992–1994, while the former study covered the more recent time interval 1998–2021. In fact, the few studies included in our comparison which extend beyond the year 2020 [15, 17] are precisely those reporting the highest LN frequencies.

The increasing LN diagnosis frequency also underlines the importance of integrating pediatric kidney biopsy reports into existing adult registries, which would prevent loss of follow-up as these patients undergo repeated biopsies as part of their disease management plan, and transition from pediatric to adult nephrology units. These data would constitute invaluable resources for future observational and interventional studies, particularly in childhood-onset LN, a condition known to have a more severe course than adult-onset LN, but for which clinical trials are scarce, and treatment schemes remain largely based on data from adult studies [8].

Limitations

Important limitations of our study include its retrospective and monocentric nature. Consequently, the data presented should not be interpreted as representing the epidemiology of kidney diseases in the general pediatric population. Similarly, comparisons with other published studies should be interpreted with caution, as observed distributions and temporal trends of diagnoses are strongly influenced by local practices, including referral and biopsy indication patterns, as well as the use of EM as a diagnostic modality. While clinical and laboratory data were available to the nephropathologist examining the kidney biopsy, these were not consistently recorded in the digital registry, apart from the general biopsy indication category, and are not included in this analysis. This limits the possibility of capturing biopsy indication patterns and their evolution over time at a more granular level. Due to transitions of patients, over time, from pediatric to adult nephrology clinics, it was not possible to obtain high-confidence follow-up data referring to treatment outcomes or the advent of kidney failure and commencement of KRT. This limits the interpretation of histopathological findings in a broader clinical context.

Strengths

Our study covers a long time period, making it possible to extract important temporal trend information related to the variables analyzed. Moreover, EM was performed in all cases where sufficient material was available, enabling detection of subtle kidney lesions, not otherwise discernible under light or immunofluorescence microscopy. EM has been recognized to contribute important information towards kidney disease diagnoses, particularly for MCD and Alport/TBMD [18], making it all the more relevant for pediatric patients, where these diagnoses are among the most frequent.

Conclusion

The findings in our pediatric cohort are largely consistent with those of other published reports, as well as with expectations given by the understanding of the mechanisms and manifestations of kidney diseases in pediatric populations. In our cohort, LN was the most common diagnosis, with overall increasing frequency across time. This is reflective of a shift in clinical practice towards a more proactive and intensive biopsy approach, in alignment with recent evidence suggesting that clinical and laboratory indicators alone are not enough to gauge the severity of kidney lesions in these patients, and underlining the importance of kidney biopsies in children with a clinical SLE diagnosis, for direct evaluation of the extent of renal involvement and navigation of treatment options.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

AKI

Acute kidney injury

CKD

Chronic kidney disease

EM

Electron microscopy

FSGS

Focal segmental glomerulosclerosis

IgAN

IgA nephropathy

IQR

Interquartile range

KRT

Kidney replacement therapy

LN

Lupus nephritis

MCD

Minimal change disease

NS

Nephrotic syndrome

SLE

Systemic lupus erythematosus

TBMD

Thin basement membrane disease

UA

Urinary abnormalities

Author contributions

I-CT and MG designed the study. AL, OL, G-CC and MG contributed to the acquisition of the data. I-CT performed the statistical analysis. All authors contributed to the interpretation of the results. I-CT wrote the first draft of the paper. All authors reviewed the manuscript critically and approved the final version for submission.

Funding

This work was supported by a grant of the Ministry of Education and Research (NUCLEU PN 23.16, contract number 10 N/2023), and a doctoral scholarship of the Carol Davila University of Medicine and Pharmacy, Bucharest.

Data availability

Due to privacy reasons, restrictions apply to the public sharing of patient-level data.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of the Victor Babeș National Institute of Pathology (nr. 120/06.02.2024). The requirement for consent to participate was waived due to the retrospective nature of the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.