Renal biopsy in diabetic patients: Histopathological and clinical correlations

Introduction: Diabetes is the leading cause of chronic kidney disease and end-stage kidney disease worldwide. A kidney biopsy in a diabetic patient must be considered when non-diabetic renal disease is suspected, such as in the presence of a rapid decline in renal function or severe unexplained proteinuria. However, the timing and criteria of a biopsy remain controversial in these patients. We aimed to identify clinical and histological markers that could help differentiate diabetic and non-diabetic renal disease and decide if this invasive approach is needed or not. Subjects and Methods: We reviewed 30 years of biopsies from diabetic patients performed at a tertiary hospital. We collected patient demographic data, biopsy indications, histological findings, and clinical and analytical data both at the moment of the biopsy and extensive followup. Based on kidney biopsy findings, patients were categorized as isolated diabetic nephropathy, non-diabetic kidney disease, or non-diabetic kidney disease superimposed on diabetic nephropathy (diabetic kidney disease). Results and Discussion: We enrolled 92 patients, mostly with type 2 diabetes, with a mean age of 62.9 ± 13.2 years. Nearly half of them had isolated diabetic nephropathy (53.3%), and 15.2% had diabetic nephropathy superimposed on non-diabetic kidney disease, comprising a total of 63 patients (68.5%) with diabetic kidney disease. Twenty-nine patients (31.5%) were considered to have non-diabetic kidney disease. These last patients were significantly less likely to need insulin therapy (p=0.002), had more frequently an acute deterioration of renal function (p=0.01), lower albumin levels (p=0.03), and a higher prevalence of microhematuria (p=0.001). We found the latter to be an independent predictor of non-diabetic kidney disease. Further, patients with the primary diagnosis of diabetic nephropathy had higher survival than those who had nondiabetic kidney disease, contradicting published data. Conclusions: The criteria for performing a biopsy in diabetic patients still lack consensus, although the priority to identify non-diabetic kidney disease prevails. We believe the non-diabetic kidney disease predictors we describe may prove helpful for determining the need for a histological assessment in diabetic patients.

Diabetes and the kidney

Diabetic renal disease is the commonest cause of end-stage renal disease (ESRD) in the Western world and is rapidly becoming the leading cause in developing countries. The following chapters provide valuable insights into the epidemiology, pathophysiology, and pathology of diabetic renal disease with a focus on the clinical presentation, diagnosis, natural history, and progression of the disease. Many patients with diabetic renal disease suffer from microvascular and macrovascular complications of diabetes, including diabetic retinopathy, neuropathy, cardiovascular, and peripheral vascular disease. The authors discuss the available treatment approaches including lifestyle, diet, and exercise. In addition, they cover the importance of maintaining healthy blood pressure and glycaemic control to improve outcomes and the pharmacological treatments available. The authors describe the range of hypoglycaemic agents now available as well as insulin treatment. Ultimately, many patients will require management of complications of diabetes. Often they develop progressive renal impairment that requires renal replacement therapy with dialysis and transplantation, which are also discussed.

Non-Diabetic Renal Disease in Type 2 Diabetic Patients with Nephropathy

Background: In diabetic patients a good proportion of nephropathy is due to nephropathy other than diabetic renal disease. The detection of superimposed primary nondiabetic renal disease in diabetic patients has an obvious prognostic and therapeutic importance. Objectives: To find out the proportion of diabetic subjects suffering from nondiabetic renal disease (NDRD) and to describe histological varieties in appropriate group. Materials and Methods: This crosssectional study was done in Department of Nephrology, Dhaka Medical College & Hospital, Dhaka from August 2015 to October 2016. Total 37 type 2 diabetic patients were selected. Renal biopsy was done and four cases were excluded due to inadequate sample. Tissue was sent for histopathology and direct immunofluorescence (DIF) examination. On the basis of histological diagnosis of biopsy reports patients were divided into three groups. Group I: Isolated NDRD, Group II: NDRD superimposed on diabetic nephropathy (mixed lesion) and Group III: Isolated diabetic nephropathy (DN). Each patient was evaluated for retinopathy from Ophthalmology department. Based on the presence or absence of retinopathy 33 patients were again divided into two groups. Group A includes patients with diabetic retinopathy (DR) and Group B includes patients without diabetic retinopathy. Results: NDRD was found in 57.6% cases, NDRD plus diabetic nephropathy (DN) in 21.2% and isolated DN in 21.2% cases. In Group A (patients with DR) NDRD, DN and mixed lesion were present in 7 (41.2%), 5 (29.4%) and 5 (29.4%) cases. In Group B (patients without DR) NDRD, DN and mixed lesion were present in 12 (75%), 2 (12.5%) and 2 (12.5%) cases respectively. p value (0.189) was not significant. Conclusion: Kidney disease other than diabetic nephropathy can occur in type 2 diabetic patients. In this study NDRD was found in high frequency. Lack of retinopathy is a poor predictor of nondiabetic kidney disease. Therefore, renal biopsy should be recommended in type 2 diabetic patients with risk factors of NDRD for accurate diagnosis, prompt initiation of disease-specific treatment and ultimately better renal outcome. J Enam Med Col 2020; 10(2): 73-78

Clinical prediction score for diagnosing non-diabetic renal disease in patients with type 2 diabetes mellitus: a cohort study

BackgroundWhen non-diabetic renal disease (NDRD) is suspected, kidney biopsy is used for definite diagnosis; however, this is not always easily available and may lead to complications. A clinical prediction score may help selecting appropriate patients for kidney biopsy. MethodsA retrospective cohort study was conducted in type 2 diabetes mellitus (T2DM) patients with atypical features of diabetic nephropathy (DN), who had kidney biopsy at Thammasat University Hospital from 2011-2019. We divided patients into NDRD alone, coexisting NDRD and DN, and DN alone, confirmed by pathological diagnosis. We developed a clinical prediction score by weighing coefficients of predictors in a multivariable logistic model. Internal validation was performed with bootstrapping.ResultsWe included 81 patients: 28 (34%) had NDRD alone, 15 (18%) had coexisting NDRD and DN, and 38 (41%) had DN alone. Primary membranous nephropathy, primary focal and segmental glomerulosclerosis (FSGS), and secondary FSGS were prevalent in any NDRD. Absence of diabetic retinopathy (DR) showed a significant association with any NDRD (OR 3.72; 95% CI, 1.28-10.8; p=0.02). The prediction score, AUC of 0.75 (95% CI, 0.63-0.86), had four predictors: duration of DM <10 years, eGFR >30 ml/min/1.73m2, HbA1c <8%, and absence of DR. Higher scores were associated with higher probability of NDRD.ConclusionsThis clinical prediction score appears to be a useful tool to determine NDRD probability. T2DM patients with atypical presentation of DN with lower scores (0-2) may defer kidney biopsy.

Clinical prediction score for diagnosing non-diabetic renal disease in patients with type 2 diabetes mellitus: a cohort study

Background: When non-diabetic renal disease (NDRD) is suspected, kidney biopsy is used for definite diagnosis; however, this is not always easily available and may lead to complications. A clinical prediction score may help selecting appropriate patients for kidney biopsy.Methods: A retrospective cohort study was conducted in type 2 diabetes mellitus (T2DM) patients with atypical features of diabetic nephropathy (DN), who had kidney biopsy at Thammasat University Hospital from 2011-2019. We divided patients into NDRD alone, coexisting NDRD and DN, and DN alone, confirmed by pathological diagnosis. We developed a clinical prediction score by weighing coefficients of predictors in a multivariable logistic model. Internal validation was performed with bootstrapping.Results: We included 81 patients: 28 (34%) had NDRD alone, 15 (18%) had coexisting NDRD and DN, and 38 (41%) had DN alone. Primary membranous nephropathy, primary focal and segmental glomerulosclerosis (FSGS), and secondary FSGS were prevalent in any NDRD. Absence of diabetic retinopathy (DR) showed a significant association with any NDRD (OR 3.72; 95% CI, 1.28-10.8; p=0.02). The prediction score, AUC of 0.75 (95% CI, 0.63-0.86), had four predictors: duration of DM <10 years, eGFR >30 ml/min/1.73m2, HbA1c <8%, and absence of DR. Higher scores were associated with higher probability of NDRD.Conclusions: This clinical prediction score appears to be a useful tool to determine NDRD probability. T2DM patients with atypical presentation of DN with lower scores (0-2) may defer kidney biopsy.

Risk factors for non-diabetic renal disease in diabetic patients

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 &lt; 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 &lt; 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 &lt; 0.001) and higher mortality (P = 0.029). In multivariate Cox analyses, older age (P &lt; 0.001), higher serum creatinine (P &lt; 0.001), higher proteinuria (P &lt; 0.001), DR (P = 0.007) and DN (P &lt; 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P &lt; 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.