Renal Histologic Analysis Provides Complementary Information to Kidney Function Measurement for Patients with Early Diabetic or Hypertensive Disease

Abstract

Background: Patients with diabetic or hypertensive kidney disease rarely undergo kidney biopsy because nephrologists commonly believe that biopsy-related risk outweighs potential benefits of obtaining histologic information to guide clinical decisions. Although kidney function is acutely regulated, histologic changes such as interstitial fibrosis, tubular atrophy, and glomerulosclerosis may represent chronic kidney damage, and thus might provide additional information about disease severity. However, whether histologic analysis provides information complementary to clinically used kidney function measurements, such as estimated glomerular filtration rate (eGFR) and proteinuria, is unclear. Methods: We performed a standardized semiquantitative histologic analysis of 859 nephrectomies obtained from individuals with or without diabetes mellitus or hypertension and varying degrees of kidney dysfunction. Changes in glomeruli, tubules, interstitium, and the vasculature were scored using 17 descriptive parameters in a standardized manner. We used multivariable linear and logistic regression analyses and unbiased, hierarchical clustering to assess associations between histologic alterations and clinical variables. Results: At chronic kidney disease (CKD) stages 3-5, eGFR estimated reasonably well the degree of glomerulosclerosis and interstitial fibrosis and tubular atrophy (IFTA). In patients with CKD stages 1-2, the degree of histologic damage was highly variable and eGFR poorly estimated the degree of such damage. Individuals with diabetes mellitus, hypertension, or Black race had significantly more glomerulosclerosis, IFTA, or both at the same eGFR level. Inclusion of glomerulosclerosis improved the kidney function decline estimation even at early disease stages. Conclusions: Histologic analysis is an important complementary method for kidney disease evaluation, especially at early disease stages. Some individuals present with relatively severe structural damage despite preserved eGFR.

Kidney biopsy-based epidemiologic analysis shows growing biopsy rate among the elderly

“…The relatively low incidence of diabetic nephropathy in our study compared to theirs may be due to the fact that performing a renal biopsy in diabetes mellitus is necessary only when an unexpectedly high rate of proteinuria or renal function decline is present. However, early stages of diabetic nephropathy may present with advanced structural damage despite the fairly normal kidney function 93 . This suggests that approaching biopsy indications with a less restrictive attitude may be advantageous and draws attention to the poor secondary prevention measures in Hungary.…”

Spatially resolved human kidney multi-omics single cell atlas highlights the key role of the fibrotic microenvironment in kidney disease progression

“…As the role of tissue elasticity in kidney function regulation is not immediately obvious( 24 ), the mechanism by which matrix accumulation (or fibrosis) affects kidney function has been controversial( 25, 26 ). Kidney function only modestly correlate with fibrosis (r = 0.4)( 18, 27 ).…”

Renal Histologic Findings in Necropsies of Type 2 Diabetes Mellitus Patients

“…In one of the few published studies including a large sample of patients in initial DN stages, Quinn et al analyzed the histologic material of nephrectomy [ 13 ], evaluating 859 samples from partial or total nephrectomies from kidney neoplasia (304 (35.4%) patients with T2DM). Their findings demonstrate that including renal histologic variables with baseline eGFR contributes to a more precise estimation of kidney function decline, especially in the early stages of DN.…”

“…The second interesting finding of our study was the high prevalence of arteriolar hyalinosis (66.7% in albuminuric and 56.3% in nonalbuminuric patients). Quinn et al also reported a high degree of arterial hyalinosis, at 32.7%, although without distinguishing between diabetic and nondiabetic patients [ 13 ]. This has also been demonstrated in kidney biopsies from DN-affected patients, where 85% displayed arteriolar hyalinosis and 60% arteriolosclerosis [ 16 ]; this condition can also affect the arteries, with a preponderant role in glomerular hemodynamic changes.…”