Risk factors for non-diabetic renal disease in diabetic patients

Abstract

Background Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. Methods Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. Results In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 ± 12.8 years, creatinine was 2.8 ± 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2–5.4) g/24 h. About 39.5% (n = 329) of patients had DN, 49.6% (n = 413) NDRD and 10.8% (n = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02–1.05, P < 0.001], microhaematuria (OR = 1.51, 95% CI: 1.03–2.21, P = 0.033) and absence of diabetic retinopathy (DR) (OR = 0.28, 95% CI: 0.19–0.42, P < 0.001) were independently associated with NDRD. Kaplan–Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P = 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P = 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P = 0.002), higher creatinine (P = 0.01) and DN (P = 0.015) were independent risk factors for mortality. Conclusions The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis.

Kidney Biopsy in Type 2 Diabetes: A Multicenter Cross-Sectional Study

“…We performed a retrospective, multicenter study including 463 patients to evaluate the association of different KB indications with NDHKD. We found that 40% of patients with T2D who underwent a KB presented NDHKD in our population, in agreement with previously published studies, where nondiabetic kidney disease was reported for 27-76% of patients [9,[23][24][25]. The frequency of NDHKD remained considerable in our study, although we assumed hypertensive nephropathy should not be considered as a nondiabetic kidney disease.…”

“…We also assessed the predictive power of individual atypical features. In apparent contradiction with the results of the KB indications analysis, hematuria, HbA1c below 7%, and duration of diabetes under 5 years were predictive of NDHKD, confirming the results of previous studies [5, 7-9, 17, 18, 24-26, 28-41]. These results might seem at odds with the absence of NDHKD among patients with presence of hematuria and short or unknown duration of diabetes which only comprised patients with stable renal function and proteinuria according to the a priori definition of biopsy indications .…”

“…The inclusion of such patients in studies on the indication and predictors of nondiabetic kidney disease in patients with T2D may be discussed. Patients with other atypical feature were explicitly excluded from 3 studies only [26][27][28] and explicitly analyzed in 3 others as extrarenal signs [24], signs of symptoms of systemic disease [9], or numerous atypical features [17]. Therefore, we purposefully emphasized this group to highlight the influence of the characteristics of these patients on the results of studies regarding the KB indications in patient with diabetes, advocating for the systematic reporting of these features when addressing this topic.…”

“…KDOQI guidelines recommend considering a non-diabetic kidney disease in the following cases: (a) signs or symptoms of other systemic disease; (b) absence of diabetic retinopathy, (c) low or rapidly decreasing estimated glomerular filtration rate (eGFR); (d) rapidly increasing proteinuria or nephrotic syndrome; (e) refractory hypertension, or (f) presence of active urinary sediment [4]. More recent studies identified short duration of diabetes and absence of retinopathy as the best predictors of nondiabetic kidney disease in patients with T2D, followed by low HbA1c, hematuria, and absence of hypertension [5][6][7][8][9]. However, nephrologists inconsistently adhere to the existing guidelines regarding KB indications in patients with T2D [10].…”

Heterogeneity in the Association Between Prediabetes Categories and Development of Impaired Renal Function in A 5-Year Follow-Up 

“…[4] It has been reported that up to 40% of patients in early stage of T2D demonstrate some degree of microvascular complication. [5] In addition, a high proportion of patients with diabetes are found to have non-diabetic renal disease (NDRD), being nephroangiosclerosis (NAS) the most frequent cause [6][7] Metabolic changes associated with diabetes lead to glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial in ammation and brosis. [5] In addition, according to various studies, one-third of adults with newly diagnosed diabetes mellitus already have kidney damage, suggesting that IRF may occur in pre-diabetic state.…”