Kidney Biopsy in Type 2 Diabetic Patients: Critical Reflections on Present Indications and Diagnostic Alternatives

Abstract

Roughly 3% of patients worldwide with a new diagnosis of type 2 diabetes mellitus (T2DM) already have an overt nephropathy at diagnosis and about 20–30% of the remaining ones develop a complication of this kind later in life. The early identification of kidney disease in diabetic patients is important as it slows its progression, which is important not only because this reduces the need for renal replacement therapy, but also because it decreases the high rate of mortality and morbidity associated with a reduction in kidney function. The increasing prevalence of type 2 diabetes and the consequent greater probability of finding different types of kidney diseases in diabetic patients frequently gives rise to overlapping diagnoses, a definition encompassing the differential diagnosis between diabetic and non-diabetic kidney disease. The issue is made more complex by the acknowledgement of the increasing frequency of presentations of what is termed “diabetic kidney disease” without relevant proteinuria, in particular in T2DM patients. Distinguishing between diabetes related and non-diabetes related forms of kidney disease in diabetic patients is not only a semantic question, as different diseases require different clinical management. However, while the urologic and macrovascular complications of diabetes, as well as overlapping parenchymal damage, can be diagnosed by means of imaging studies, often only a kidney biopsy will make a differential diagnosis possible. In fact, the coexistence of typical diabetic lesions, such as nodular glomerulopathy or glomerulosclerosis, with different glomerular, vascular and tubulo-interstitial alterations has been extensively described, and an analysis of the dominant histological pattern can contribute to determining what therapeutic approach should be adopted. However, due to the high frequency of kidney diseases, and to the fact that T2DM patients are often affected by multiple comorbidities, a kidney biopsy is not generally performed in T2DM patients. What follows is a review aiming to discuss the diagnostic work-up, on the base of clinical, laboratory and imaging criteria, and evaluate the present indications and alternatives to renal biopsy.

Mitochondria in Diabetic Kidney Disease

“…In contrast with the DKD with albuminuria, the pathogenesis of the DKD without albuminuria involves macrovascular lesions of intrarenal arteries. This hypothesis is based on the association with T2D [ 34 ] and several cardiovascular risk factors in addition to hyperglycemia such as central obesity, hyperlipidemia, and hypertension [ 35 ]. The presence of tubulointerstitial lesions including inflammation, tubular atrophy, and an accelerated tubular senescence-like phenotype [ 36 ] are reported independent predictors of eGFR decline [ 37 , 38 ].…”

Predictors of cardio-kidney complications and treatment failure in patients with chronic kidney disease and type 2 diabetes treated with SGLT2 inhibitors

“…To address this limitation in identifying DKD, validated algorithms for identification of T2D patients from inpatient, outpatient, and prescription claims, as well as two laboratory values indicating kidney disease to identify CKD patients, were used. Nonetheless, DKD can only be accurately defined by histopathologic screening of the kidney [ 27 ]. Second, not all important comorbidities or risk factors can be accurately ascertained within claims data, such as a patient’s smoking status, body mass index, and other CKD symptoms (e.g., poor appetite, weakness, or itching).…”

Role of Zinc in Diabetic Kidney Disease

“…Kidney biopsy is of pivotal importance for a correct diagnosis but also for defining prognosis, especially in the presence of heavy proteinuria or its rapid onset [ 53 ]. A timely correction of risk factors for DKD progression and a personalized therapeutic approach are fundamental in decreasing the impact of its complications and to reduce the risk of ESRD [ 54 , 55 ].…”