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Suzuki Akihiko; Moriya Tatsumi; Hayashi Akinori; Matsubara Madoka; Miyatsuka Takeshi: Arteriolar Hyalinosis Predicts the Onset of Both Macroalbuminuria and Impaired Renal Function in Patients with Type 2 Diabetes. Nephron DOI 10.1159/000535875
The morphological characteristics found in kidneys biopsied of patients with type 2 diabetes (T2DM) and overt nephropathy that predict future progression are increasingly receiving much attention, but our knowledge of the predictive power of such histological lesions in early (incipient) nephropathy is very uncertain and understudied.
Suzuki and colleagues have conducted an observational, prospective cohort study in 35 patients with T2DM: 12 women and 23 men (average duration of T2DM of 11 ± 7 years) with normal or moderate albuminuria (30–299 mg/day) and an eGFR of >60 mL/min/1.73 m2 (mean 93 ± 18 mL/min/1.73 m2). The follow-up was for at least 5 years (18 ± 6 years). The “endpoints” of the study were overt albuminuria (>300 mg/day) AND an eGFR of <60 mL/min/1.73 m2. No re-biopsies were performed. Arteriolar hyalinosis (AH) was assessed semi-quantitatively. Treatment modalities were not described in detail, but adequate blood pressure control was a goal. Apparently, SGLT2 inhibitors were not used.
The annual risk of a decline in eGFR was correlated with the degree of AH (r2 = 0.16, p = 0.011) in a regression analysis. The effect of AH was independent of other conditional variables. The development of albuminuria of >300 mg/day AND an eGFR <60 mL/min/1.73 m2 was also independently associated with the degree of AH, but not the isolated development of an eGFR of <60 mL/min/1.73 m2 alone.
Other glomerular morphometric indices (such as glomerular volume, GBM thickening, mesangial matrix increase) did not correlate with the primary endpoint. Podocytopenia was not examined. Glomerular ischemic pathology was not observed. Interestingly, 45% of the patients who progressed to an eGFR <60 mL/min/1.73 m2 did not have an increase in albuminuria to >300 mg/day (non-albuminuric diabetic nephropathy). These very provocative findings in a small Japanese cohort need to be confirmed in a larger, more ethnically diverse cohort. Perhaps the ongoing Precision Medicine Project in the USA, involving early diabetic nephropathy, will provide this information. The lack of data concerning concomitant standard-of-care therapy is an unfortunate weakness of this otherwise well-done study. It highlights the frequency of non-albuminuric diabetic nephropathy and provides a rationale for more focus on the poorly understood pathogenesis of the AH lesion. We know next to nothing about the mechanistic link of AH and progressive nephropathy in diabetic patients.
