See Article on Pages 91-101
The usefulness of kidney biopsy in patients with type 2 diabetes mellitus (T2DM) remains debated. Diabetic kidney disease (DKD) is traditionally diagnosed using clinical markers such as a long history of diabetes mellitus (DM), retinopathy, and gradually increasing proteinuria. Despite the presence of atypical clinical features, kidney biopsies are not widely performed, primarily due to reluctance among physicians, even when nondiabetic causes of renal dysfunction are suspected. This is in contrast to the clear consensus for performing kidney biopsies in nondiabetic patients with renal issues.
The prognosis for T2DM patients is often unpredictable. While many follow a typical progression, some experience rapid declines, including acute kidney injury [
1]. Factors such as uncontrolled hyperglycemia, hypertension, heavy proteinuria, and exposure to nephrotoxic drugs have been implicated. However, some patients deteriorate without these factors. Determining the exact cause of rapid renal function decline without a kidney biopsy is challenging. Biopsies can identify curable non-DKD (NDKD), especially in patients with atypical features.
In this issue, Kim et al. [
2] highlight the utility of kidney biopsies in T2DM patients. Their study found a higher proportion of NDKD (61.6%) and mixed DKD/NDKD (9.3%) than previously reported, likely due to selection bias. Existing literature suggests the prevalence of NDKD ranges from 15% to 40%, but exact figures remain unclear. Mazzucco et al. [
3] demonstrated that the criteria for performing kidney biopsies significantly impact the identification of NDKD. In their study, biopsies were performed under two different policies: restricted (limited to cases with strong indications) and unrestricted (applied more broadly). They found a higher prevalence of NDKD in the restricted group, while the mixed DKD/NDKD type was more common in the unrestricted group. In this study, the frequency of renal pathology was 57 in DKD only, 30 in ischemic diseases, and 111 in NDKD only or mixed lesions among 198 patients, showing a very high rate of nondiabetic lesions. These results show how physician decisions and biopsy indications can profoundly affect diagnostic outcomes.
Kim et al. [
2] also found that immunoglobulin A nephropathy was the most common cause of NDKD, followed by focal segmental glomerulosclerosis. Minimal change disease was the most prevalent in mixed-type cases, and tubulointerstitial nephritis was also common. Both conditions are relatively responsive to immunosuppressants like corticosteroids. Given the poor prognosis without treatment, timely administration of immunosuppressants is crucial. However, corticosteroids can exacerbate hyperglycemia and increase infection risk, necessitating a careful risk-benefit analysis. Recent studies suggest that low-dose corticosteroid combined with mycophenolate might offer a safer alternative, achieving high remission rates with fewer complications [
4]. Although they did not include patients with DM, alternative therapies can be considered to reduce complication risks in T2DM patients.
No specific biomarkers or treatment protocols for NDKD in T2DM patients have been established. Prospective cohort studies, such as the HEROIC study, are ongoing and aim to provide better differential markers prior to biopsy [
5]. The HEROIC study involves kidney biopsies in patients with an eGFR >30 mL/min/1.73 m
2, a urine albumin-to-creatinine ratio ≥30 mg/mmol, or an eGFR decline of ≥5 mL per year. These studies could provide the tool to predict differentiation between DKD and NDKD before kidney biopsy.
In conclusion, while kidney biopsy in T2DM patients remains debated, it can provide valuable diagnostic, therapeutic, and prognostic information. Despite its invasive nature, which limits widespread application, a stepwise approach based on clinical features, as suggested by Hsieh et al. [
6], could be appropriate. This approach includes assessing proliferative diabetic retinopathy, DM duration, and hematuria presence. Before a kidney biopsy, the first step should be a thorough assessment of the patient’s condition. Patients with poor conditions, such as uncontrolled hyperglycemia, hypertension, poor hygiene, and poor compliance to treatment, should be excluded. For patients who are expected to tolerate immunosuppression, kidney biopsy could be considered to improve outcomes in those with NDKD.