Total Nephron Number and Single-Nephron Parameters in Patients with IgA Nephropathy

Abstract

Background: Single nephron dynamics in progressive IgA nephropathy (IgAN) have not been studied. We applied novel methodology to explore single nephron parameters in IgAN. Methods: Non-globally sclerotic glomeruli (NSG) and globally sclerotic glomeruli (GSG) per kidney were estimated using cortical volume assessment via unenhanced computed tomography and biopsy-based stereology. Estimated single-nephron GFR (eSNGFR) and urine protein excretion (SNUPE) were calculated by dividing eGFR and UPE by the number of NSG. Associations with CKD stage and clinicopathologic findings were cross-sectionally investigated. Results: This study included 245 IgAN patients (mean age 43 y, 62% male, 45% on renin-angiotensin aldosterone system [RAAS] inhibitors pre-biopsy) evaluated at kidney biopsy. CKD stages were 10% CKD1, 43% CKD2, 19% CKD3a, 14% CKD3b and 14% CKD4-5. With advancing CKD stage, NSG decreased from mean 992,000 to 300,000 per kidney whereas GSG increased from median 64,000 to 202,000 per kidney. In multivariable models, advancing CKD stage associated with lower numbers of NSG, higher numbers of GSG, and lower numbers of GSG+NSG, indicating potential resorption of sclerosed glomeruli. In contrast to the higher mean glomerular volume and markedly elevated SNUPE in advanced CKD, the eSNGFR was largely unaffected by CKD stage. Lower SNGFR associated with Oxford scores for endocapillary hypercellularity and crescents whereas higher SNUPE associated with segmental glomerulosclerosis and tubulointerstitial scarring. Conclusions: SNUPE emerged as a sensitive biomarker of advancing IgAN. The failure of eSNGFR to increase in response to reduced number of functioning nephrons suggests limited capacity for compensatory hyperfiltration by diseased glomeruli with intrinsic lesions.

X-Ray-Based 3D Histopathology of the Kidney Using Cryogenic Contrast-Enhanced MicroCT

“…The analysis showed a significant increase in glomerular volume between cortical and juxtamedullary glomeruli in healthy kidneys. This observation has already been made by others [ 43 – 46 ]. However, there is still debate whether this change in size is inherent or induced by various factors such as aging, obesity, or glomerulosclerosis.…”

Single-Nephron GFR in Different Glomerular Basement Membrane Stages of Membranous Nephropathy

“… 18 This technical advancement enabled us to estimate the SNGFR in patients with kidney disease, for which the administration of contrast media is generally contraindicated. 19 – 21 In this study, we aimed to assess single-nephron parameters, including SNGFR and single-nephron urinary protein excretion (SNUPE), in patients with MN with different Ehrenreich and Churg (EC) stages for GBM lesions.…”

Single-nephron assessment of urate excretion in patients with IgA nephropathy

“…We recently established a method to estimate the total nephron number in clinical practice and reported nephron number estimates in patients with IgAN [ 3 ]. As a subanalysis of our data, we estimated the urinary urate excretion per nephron in patients with IgAN.…”