Study Reveals Factors Associated with Non-DKD on Kidney Biopsy in Patients with Diabetes

Findings from a recent study are providing clinicians with an overview of clinical parameters associated with nondiabetic kidney disease (non-DKD) in the setting of diabetes, describing when kidney biopsy should be considered in this patient population to capture all proteinuria and kidney dysfunction etiologies.¹

Leveraging data from more than 1000 patients with diabetes and kidney biopsy from the Cleveland Clinic Kidney Biopsy Epidemiology Project (CCKBEP), the study showed 63% of patients had findings in addition to DKD on biopsy, additionally identifying lack of retinopathy, lower hemoglobin A1c levels, preserved estimated glomerular filtration rate (eGFR), microalbuminuria, and lower degree of random urine protein-creatinine ratio (UPCR) as factors associated with non-DKD.¹

A serious complication of type 1 diabetes and type 2 diabetes, diabetic nephropathy, or DKD, affects 1 in 3 people living with diabetes in the US and is a predominant etiology of kidney failure. Kidney failure cases attributed to DKD are often diagnosed without the confirmation of kidney biopsy, suggesting the need for a better understanding of factors necessitating kidney biopsy in patients with diabetes to identify other potential concurrent actionable kidney conditions.^1,2

“Although clinical judgment in this setting is key and continues to be standard practice, it is important for clinicians to know which factors ensure/prompt kidney biopsy in a patient with diabetes,” Shane Bobart, MD, of the division of kidney diseases in the department of medicine at Houston Methodist Hospital, and colleagues wrote.¹ “Currently, factors such as rapidly declining kidney function, unusual clinical course, positive serology, systemic diseases or active urinary sediment prompt biopsy, but this is the practice for most kidney diseases. Additionally, there is a lack of data to guide the decision on kidney biopsy that is grounded in validated statistical models.”

To identify factors associated with the diagnosis of non-DKD in patients with diabetes, investigators conducted a retrospective cohort study of patients enrolled in the CCKBEP, a catalog of biopsy diagnoses as well as clinical and demographic data of all patients who had a kidney biopsy performed/reviewed at the Cleveland Clinic from January 2015 to September 2021. In this population, investigators identified patients with ICD-10 code data available in the electronic medical record indicating a history of diabetes.¹

Each biopsy report underwent examination by a nephropathologist as part of clinical care affiliated with the Cleveland Clinic, following a standardized protocol encompassing procedures for light microscopy as well as immunofluorescence and electron microscopy. Investigators defined DKD as diffuse mesangial sclerosis with glomerular basement membrane thickening, with or without mesangial nodularity on light microscopy.¹

Of 4125 patients with native kidney biopsies in the CCKBEP, 3500 had ICD-10 code data available and investigators identified 1268 (36.2%) with an ICD-10 code for diabetes. Of these patients, 462 (36.4%) had DKD alone, 675 (53.2%) had non-DKD alone, and 105 (8.3%) had both DKD and non-DKD. An additional 26 (2.1%) patients were either normal or nondiagnostic and were thus excluded from the final analysis.¹

Among the cohort (n = 1242), the median (IQR) age was 63 (Interquartile range [IQR], 53-71) years, 58.8% of patients were male, 66.3% were White, and 93.7% had hypertension. The median hemoglobin A1c value was 6.7% (IQR, 6.0%-8.1%), and the median serum creatinine level was 2.5 (IQR, 1.6-3.9mg/dL) mg/dL.¹

Among those with non-DKD, investigators noted the most common diagnoses were focal segmental glomerulosclerosis (24%), global glomerulosclerosis otherwise not specified (13%), acute tubular necrosis (9%), IgA nephropathy (8%), antineutrophil cytoplasmic antibody vasculitis (7%), and membranous nephropathy (5%).¹

Upon analysis, factors associated with having non-DKD on biopsy were having no retinopathy (vs retinopathy) (adjusted odds ratio [aOR], 3.98; 95% CI, 2.69-5.90), lower A1c levels (<7% vs≥7%) (aOR, 3.08; 95% CI, 2.16-4.39), greater eGFR (≥60 vs<60mL/min/1.73m2) (aOR, 2.39; 95% CI 1.28-4.45), microalbuminuria (<300 vs macroalbuminuria ≥300 [mg/g]) (aOR; 2.94; 95% CI, 1.84-4.72), and lower protein-creatinine ratio on random urine sample (<3 vs≥3mg/mg) (aOR; 1.80; 95% CI, 1.24-2.61).¹

Investigators outlined multiple limitations to these findings, including the retrospective study design; inherent limitations to the data available for analysis; and potential selection bias in the cohort.¹

“Our study has identified several clinical parameters associated with finding non-DKD in the setting of diabetes, such as lack of retinopathy, lower hemoglobin A1c levels, preserved eGFR, microalbuminuria (vs macroalbuminuria), and lower degree of random UPCR. This provides valuable information for clinicians on when kidney biopsy should be considered among patients with diabetes to capture all etiologies of proteinuria and kidney dysfunction,” investigators concluded.¹

References

1. ^{Kwon AG, Sawaf H, Portalatin G, et al. Kidney Biopsy Findings Among Patients With Diabetes in the Cleveland Clinic Kidney Biopsy Epidemiology Project. Kidney Medicine. doi:10.1016/j.xkme.2024.100889}
2. ^{Mayo Clinic. Diabetic nephropathy (kidney disease). Diseases & Conditions. October 24, 2023. Accessed September 25, 2024. https://www.mayoclinic.org/diseases-conditions/diabetic-nephropathy/symptoms-causes/syc-20354556}