INTRODUCTION
Renal biopsy has remained an essential tool for diagnosing and characterizing glomerular diseases for decades owing to the lack of validated and available substitute diagnostic biomarkers with high sensitivity and specificity. The most promising biomarkers have not yet been implemented in routine clinical practice because of insufficient validation in large cohorts, or because limited access or high costs prevent global implementation[1]. Consequently, most of the proposed biomarkers have not been incorporated into the current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for managing glomerular diseases. Consequently, renal biopsy has maintained its relevance, and its clinical utility remains highly valuable, providing definitive histological data that can guide the diagnosis, management, and prognostication of kidney diseases. Moreover, renal histology can lead to changes in treatment decisions in approximately 40% of cases[2,3].
Most epidemiological studies on glomerular diseases involve large patient series that analyze the different histological patterns observed. These studies have shown heterogeneous results across regions, potentially influenced by demographic, genetic, environmental, and temporal factors, as well as other aspects such as variability in referral and biopsy policies between different countries and within regions[4,5]. In a recent issue of this journal, Puspitasari et al[6] described the frequency of renal biopsies performed and the histological patterns identified over six consecutive years, covering an initial period before the coronavirus disease 2019 (COVID-19) pandemic and a second period during and after the pandemic. Their results highlighted a dramatic reduction in the number of biopsies performed after the onset of the pandemic (2020), with lupus nephritis (LN) being the most frequently observed histological finding throughout the study period, accounting for one-third of the cases, followed by minimal change disease (MCD). After the onset of the COVID-19 pandemic, an increase in the proportion of biopsies showing LN and a significant reduction in biopsied MCD cases were observed compared with the pre-pandemic period. Although LN exhibited a frequency pattern similar to that reported in middle-income countries, where LN is the most common secondary glomerular disease in biopsies, a high proportion of MCD cases stood out[7]. As the authors noted, this high number of biopsies showing MCD might be explained by the over-representation of young individuals in the sample (40% being aged < 25 years), potentially at the expense of older individuals. There may also be some degree of overestimation of MCD diagnoses, differentiating MCD from focal segmental glomerulosclerosis can be challenging in early stages[8].
The significant changes observed in the frequencies of LN and MCD between the pre-and during/post-pandemic periods have not been consistently demonstrated in other studies[9]. These variations may reflect the influence of different biopsy criteria on renal biopsy data. During the periods of lockdown, social distancing, uncertainty, high care demand, and limited hospital bed availability, histological diagnostic efforts may have prioritized nephritic clinical phenotypes over nephrotic ones, which may have been treated empirically.
The correlation between the clinical and histopathological diagnoses in nephrology is critical, especially considering the nuances associated with nephritic and nephrotic syndromes. The predominance of nephritic syndrome in the clinical indications for biopsy in the study by Puspitasari et al[6], despite the higher prevalence of nephrotic syndromes reflected in the final diagnoses, raises important questions regarding clinical decision-making. Interestingly, a substantial proportion (80%) of the biopsies were diagnosed with nephrotic syndrome, and histological findings revealed a significant prevalence of nephrotic syndrome, primarily MCD and focal segmental glomerulosclerosis. This discrepancy indicates a potential gap in the understanding or identification of nephrotic syndrome manifestations, even among nephrologists, which may lead to an underestimation of nephrotic conditions that require histological evaluation.
Over the past two decades, significant progress has been made in elucidating the mechanisms underlying the pathogenesis of various glomerular diseases, thereby enhancing the development of diagnostically useful biomarkers (Figure 1). The shift towards utilizing biomarkers, as outlined in the KDIGO guidelines, reflects an evolving approach for diagnosing and managing kidney diseases. This shift is becoming increasingly essential owing to the potential risks associated with invasive diagnostic strategies, such as biopsies, and the need for shorter diagnostic times. The discovery and recommendation to measure serum antibodies against the phospholipase A2 receptor (PLA2R) in cases of nephrotic syndrome suggests a move towards more targeted treatment interventions, potentially reducing the need for invasive biopsy procedures[10]. In addition to the anti-PLA2R antibodies used for diagnosing membranous nephropathy, the detection of autoantibodies against thrombospondin type 1 domain-containing 7A and neural epidermal growth factor-like 1 may prove useful[11,12]; these antibodies are present in 10% and 16% of the cases of anti-PLA2R-negative membranous nephropathy, respectively. The recent identification of anti-nephrin antibodies as potential biomarkers for podocyte diseases, particularly in diagnosing MCD, has made significant advances, although further validation and confirmation of these findings are necessary[13,14]. As the field of nephrology continues to evolve, it is likely that other serological markers (such as anti-double-stranded DNA antibodies for LN, anti-PLA2R antibodies for membranous nephropathy, and ANCAs for microscopic polyangiitis) will similarly influence clinical practice and renal biopsy decisions. Consequently, it is crucial to discover, research, and validate high-performance biomarkers to ensure that they are affordable for most centers worldwide.
Figure 1 Timeline of the development of relevant biomarkers (useful or promising) for the diagnosis of primary glomerular diseases.
Gd-IgA1: Galactose-deficient IgA1; PLA2R: M-type phospholipase A2 receptor; THSD7A: Thrombospondin type 1 domain containing 7A; DNAJB9: DnaJ homolog subfamily B member 9; NELL-1: Neural epidermal growth factor-like 1 protein.
Ultimately, the clinical diagnosis remains paramount in guiding the decision to perform a biopsy. Greater awareness and education regarding the different presentations of nephrotic and nephritic syndromes, along with the integration of emerging biomarkers into clinical practice, can lead to improved patient outcomes. Developing protocols that balance clinical evaluation with serological testing may streamline the diagnostic process, ensuring that patients receive timely and appropriate management of their renal condition.
The COVID-19 pandemic caused serious direct and indirect adverse health outcomes in nephrologic patients, who faced collateral reductions in access to care based on the pandemic's impact on healthcare facilities in each region. In some countries, significant reductions were observed in access to dialysis as well as in outpatient and inpatient nephrologic care. This resulted in a reduction in the number of dialysis stations, an increase in absenteeism rates, a higher patient-to-nurse ratio, and deterioration of patients' laboratory and dialysis adequacy parameters[15,16]. In addition, there was a global decline in the number of transplants and donations from living and deceased donors[17-19]. Notably, in Europe, the kidney transplantation rate decreased by 22.5%, affecting most countries[19]. This decline is particularly critical, as patients on the waiting list face greater risks of complications and mortality than those who receive transplants. Similar to the findings of Puspitasari et al, several reports have noted a marked reduction in the number of renal biopsies performed immediately after the onset of the pandemic, followed by an increase in the later period (Figure 2)[6,17,20,21]. The COVID-19 pandemic and subsequent lockdowns significantly impacted various aspects of care for nephrology patients. Ensuring sustained access to optimal care for patients requiring renal replacement and complex procedures in response to future large-scale events is crucial.
Figure 2 Trend of number of biopsies from 2017 to 2022 at Dr. Sardjito General Hospital.
Citation: Puspitasari M, Wardhani Y, Sattwika PD, Wijaya W. Patterns of kidney diseases diagnosed by kidney biopsy and the impact of the COVID-19 pandemic in Yogyakarta, Indonesia: A single-center study. World J Nephrol 2024; 13(4): 100087. Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc.
