Kidney Week

Abstract: TH-OR57

Single-Nephron Dynamics in Patients with Overt Diabetic Nephropathy

Session Information

• Improving Clinical Outcomes in Diabetic Kidney Disease
  November 02, 2023 | Location: Room 121, Pennsylvania Convention Center
  Abstract Time: 05:24 PM - 05:33 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Miura, Akane, Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

Akane Miura

• Okabe, Masahiro, Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

Masahiro Okabe,

• Sasaki, Takaya, Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

Takaya Sasaki,

• Okabayashi, Yusuke, Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

Yusuke Okabayashi,

• Haruhara, Kotaro, Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

Kotaro Haruhara,

• Tsuboi, Nobuo, Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

Nobuo Tsuboi,

• Yokoo, Takashi, Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

Takashi Yokoo,

Background

In diabetic nephropathy (DN), total glomerular hyperfiltration is observed from early stage of the disease, and glomerular filtration rate (GFR) decreases with a marked increase in albuminuria, leading to renal failure. In the clinical course of such overt DN, the single-nephron GFR (SNGFR) is thought to be dysregulated with a decrease in the number of functioning nephrons. However, the single-nephron dynamics has not been studied in human DN due to technical difficulties. We applied novel methodology to explore single-nephron dynamics in DN.

Methods

The number of non-globally sclerotic glomeruli (N_NSG) per kidney was estimated using cortical volume assessment via unenhanced computed tomography and biopsy-based stereology. Mean glomerular volume (MGV) was calculated from the measured area of glomerular tufts. SNGFR and single-nephron urinary protein excretion (SNUPE) was calculated by dividing estimated GFR and UPE by the total number of N_NSG per body (per kidney x 2). Single-nephron parameters (MGV, SNGFR and SNUPE) were compared among CKD stages.

Results

This study included 86 patients with DN evaluated at kidney biopsy (median age 55 [quartile 46-67] years, 84% male, HbA1c 6.6 [5.9-7.3] %, 53% with nephrotic syndrome, and 64% on renin-angiotensin-system inhibitors prebiopsy). CKD stage were 16% CKD1+2, 28% CKD3a, 25% CKD3b, 19% CKD4, and 12% CKD5. With advancing CKD stage, sclerotic glomerular lesions increased, whereas N_NSG decreased from median 780,900 to 251,200 per kidney. In contrast to the higher MGV and elevated SNUPE, SNGFR was markedly decreased in patients with advanced CKD (Figure 1).

Conclusion

Despite residual glomerular hypertrophy, the progressive decrease in SNGFR with decreased number of functioning nephrons in advanced stage DN suggests glomerular filtration failure due to progressive glomerulosclerotic lesions and reduced filtration surface.