Non-diabetic Renal Disease In Patients Research Articles

#1626 The role of sodium-glucose cotransporter 2 inhibitors in diabetic nephropathy and non diabetic renal disease in diabetes mellitus type 2 patients

Abstract Background and Aims Diabetes Mellitus type 2 (DM2) leads to chronic kidney disease in a 30-40% of diabetic patients and it is the major cause of end stage renal disease (ESRD). The clinical course of diabetic kidney disease is very heterogeneous and there is a lack of agreement between clinical parameters and renal histology. Besides, lesions of non-diabetic kidney disease (NDRD) can coexist with lesions of diabetic nephropathy (DN) in two-thirds of kidney biopsies in patients with diabetes. There is not a specific treatment against diabetic kidney disease, treatment based in the blockade of renin-angiotensin-aldosterone system has demonstrated a delay of kidney function decline but the diabetic kidney disease is still the main cause of renal replacement by dialysis. Recently, a new class of oral glucose -lowering drugs, sodium-glucose cotransporter 2 (SGLT2) inhibitors, have shown beneficial effects into cardiovascular protection and chronic kidney disease in diabetic patients but it is not clear the beneficial effect in DN. The aim of this study is to evaluate the role of SGLT2 inhibitors in diabetic patients with DN biopsy-confirmed and compare with a group of diabetic patients with NDRD (DN and superimposed non diabetic renal disease lesions, NDRD). Method This is a retrospective study with DM2 patients and kidney biopsy performed. Patient demographic characteristics were recorded and diagnosis of Hypertension, duration of DM2, presence or absence of diabetic retinopathy (DR), macrovascular disease and treatment with renin–angiotensin– aldosterone system blockers (RAASB), oral hypoglycaemic agents, insulin, and aldosterone antagonists. Histological lesions were recorded according to the pathologic classification of DN. Renal function was based on estimated filtration rate CKD-EPI (eGFR mil/min/m2), the urine albumin-creatinine ratio (UACR mg/gr) and the 24 h proteinuria (g/24 h). Diabetic patients were classified according to the kidney biopsies in DN and NDRD. The follow up was assessed at the time of sodium-glucose cotransporter 2 (SGLT2) inhibitors started, 6, 12 and 24 months. Results A total of 64 DM2 patients with kidney biopsy were included in the study. Basal characteristics are summarized in Table 1. DN was diagnosed in 47% and NDRD in 53% of DM2 patients. DM2 patients with NDRD were older (64 ± 10 vs 70 ± 10, p = 0.017), and with more macrovascular disease than patients with DN, 6 (20%) vs 15 (44%), p = 0.04. Instead, DM2 patients with DN showed higher uACR levels than NDRD (2355 ± 2540 vs 706 ± 730, p = 0.02). A 40% of DM2 patients with DN were classified in nodular sclerosis class III of glomerular classification of DN. Interstitial fibrosis and tubular atrophy score were higher in DN versus NDRD patients, (interstitial fibrosis 12 (40%) vs 3 (9%), p = 0.006, tubular atrophy 10 (33%) vs 3 (9%), p = 0.02, Table 2. At the end of follow up, 20% of DM2 patients developed ESRD. According SGLT2 inhibitors treatment, a higher proportion of ESRD and death were observed in DM2 patients without SGLT2 inhibitors than patients with SGLT2 inhibitors, ESRD 11 (39%) vs 2 (6%), p = 0.001, death 9 (32%) vs 4 (11%), p = 0.03. Serum creatinine levels were lower in DM2 patients with SGLT2 inhibitors (118 ± 63.7 vs 203 ± 80.7, p = 0.001), but no differences was observed in uACR between groups. A significant reduction in serum creatinine levels with better eGFR were observed in both groups (DN and NDRD) under SGLT2 inhibitors comparing to group without SGLT2 inhibitors, serum creatinine levels 124 ± 78 vs 236 ± 83, p = 0.008, 107 ± 40 vs 201 ± 110, p = 0.02, and eGFR mil/min/m2 60.9 ± 27.5 vs 25.1 ± 7.2, p = 0.004, 62.6 ± 21.2 vs 33.7 ± 16.2, p = 0.005, Table 3. Conclusion A higher proportion of DM2 showed NDRD lesions in kidney biopsy. Treatment with SGLT2 inhibitors reduced progression of chronic renal disease in DN and NDRD DM2 patients. A reduced progression to ESRD and death were also observed in NDRD DM2 patients with SGLT2 treatment.

Optical coherence tomography angiography for the differentiation of diabetic nephropathy from non-diabetic renal disease

BackgroundTo provide a new non-invasive method for the differentiation of diabetic nephropathy (DN) from non-diabetic renal disease (NDRD) by assessing retinal microstructure using optical coherence tomography angiography (OCTA). MethodsOCTA parameters were recorded and their relationship with DN was analysed. A differential diagnosis regression model for DN was established, and the diagnostic efficiency was evaluated. ResultsBased on the pathological results of renal biopsy, 31 DN patients and 35 NDRD patients were included. Multivariate logistic regression analysis showed that DN was independently associated with the following parameters: 15.3 mm−1 ≤ vessel density (VD) full < 17.369 mm−1 (odds ratio [OR]=8.523; 95% confidence interval [CI]=1.387–52.352; P = 0.021), VD full < 15.3 mm−1 (OR=8.202; 95% CI=1.110–60.623; P = 0.039), DM duration > 60 months (OR=7.588; 95% CI=1.569–36.692; P = 0.012), and estimated glomerular filtration rate < 60 mL/min/1.73 m2 (OR=24.484; 95% CI=4.308–139.142; P < 0.001). The area under the receiver operating characteristic curve was 0.911, indicating a high diagnostic efficiency. ConclusionsVD full < 17.369 mm−1, DM duration > 60 months, and eGFR < 60 mL/min/1.73 m2 may indicate the presence of DN. OCTA may be an effective non-invasive method for identifying DN and NDRD.

The Prevalence and Clinicopathological Spectrum of Nondiabetic Renal Disease in Patients with Diabetes in a Tertiary Care Center

Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM), leading to end-stage renal disease. A wide spectrum of nondiabetic renal diseases (NDRDs) is reported in type 2 DM. We retrospectively reviewed the medical records of patients with type 2 DM who underwent a kidney biopsy from September 2019 to November 2021 at our center. Patients were grouped as having isolated DN, isolated NDRD, or mixed NDRD with underlying DN. According to the 379 renal biopsies performed during the study period, 57 patients had DM. The prevalence of DN, isolated NDRD, and combined pathologies was 36.8%, 35.1%, and 28.1%, respectively. The most common NDRD was infection-related glomerulonephritis (IRGN) (50.0%), followed by membranous nephropathy (3.0%), focal segmental glomerulosclerosis (10%), pyelonephritis (10%), minimal change disease (1.8%), fibrillary glomerulonephritis (1.8%), and ANCA-associated vasculitis (1.8%). The most common pathological finding of NDRD in the mixed group was IRGN (56.3%), followed by acute tubular injury (31.3%). The duration of DM was significantly shorter (4.8 ± 2.3 years vs. 9.7 ± 3.3 years, P = 0.035) in NDRD patients compared with patients with DN. NDRD was observed in 15% and mixed lesions in 25% of patients, with concomitant diabetic retinopathy (P = 0.029). We conclude that with increasing evidence of NDRD even in patients with DN, careful application of renal biopsies in diabetic patients would assist in the early diagnosis and institution of specific therapy for NDRD to ensure better patient and renal survival.

Identification of a Non-Invasive Urinary Exosomal Biomarker for Diabetic Nephropathy Using Data-Independent Acquisition Proteomics.

Diabetic nephropathy (DN), as the one of most common complications of diabetes, is generally diagnosed based on a longstanding duration, albuminuria, and decreased kidney function. Some patients with the comorbidities of diabetes and other primary renal diseases have similar clinical features to DN, which is defined as non-diabetic renal disease (NDRD). It is necessary to distinguish between DN and NDRD, considering they differ in their pathological characteristics, treatment regimes, and prognosis. Renal biopsy provides a gold standard; however, it is difficult for this to be conducted in all patients. Therefore, it is necessary to discover non-invasive biomarkers that can distinguish between DN and NDRD. In this research, the urinary exosomes were isolated from the midstream morning urine based on ultracentrifugation combined with 0.22 μm membrane filtration. Data-independent acquisition-based quantitative proteomics were used to define the proteome profile of urinary exosomes from DN (n = 12) and NDRD (n = 15) patients diagnosed with renal biopsy and Type 2 diabetes mellitus (T2DM) patients without renal damage (n = 9), as well as healthy people (n = 12). In each sample, 3372 ± 722.1 proteins were identified on average. We isolated 371 urinary exosome proteins that were significantly and differentially expressed between DN and NDRD patients, and bioinformatic analysis revealed them to be mainly enriched in the immune and metabolic pathways. The use of least absolute shrinkage and selection operator (LASSO) logistic regression further identified phytanoyl-CoA dioxygenase domain containing 1 (PHYHD1) as the differential diagnostic biomarker, the efficacy of which was verified with another cohort including eight DN patients, five NDRD patients, seven T2DM patients, and nine healthy people. Additionally, a concentration above 1.203 μg/L was established for DN based on the ELISA method. Furthermore, of the 19 significantly different expressed urinary exosome proteins selected by using the protein-protein interaction network and LASSO logistic regression, 13 of them were significantly related to clinical indicators that could reflect the level of renal function and hyperglycemic management.

Assessment of the Added Value of Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging in Identifying Non-Diabetic Renal Disease in Patients With Type 2 Diabetes Mellitus.

Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear. To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM. Prospective. Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD). 3 T/ T2 weighted imaging (T2WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). The parameters derived from IVIM-DWI (true diffusion coefficient [D], pseudo-diffusion coefficient [D*], and pseudo-diffusion fraction [f]) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy [DR], fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively. Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant. The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively). The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM. 2 TECHNICAL EFFICACY: Stage 2.

Empagliflozin attenuates the renal tubular ferroptosis in diabetic kidney disease through AMPK/NRF2 pathway.

Renal tubular damage plays a key role in the pathogenesis of diabetic kidney disease (DKD), and one of the main pathological process associated with DKD in diabetic mice is the ferroptosis, a novel form of cell death caused by iron-dependent lipid peroxidation. Several researches suggested that empagliflozin may treat renal injury, but its effects on diabetic-related ferroptosis and underlying mechanisms were not fully elucidated. In this study, the influence of empagliflozin on renal injury was evaluated in vivo and in vitro in a mouse model and in high-glucose (HG) or Erastin-stimulated renal HK-2cell line, respectively. Ferroptosis-related markers were assessed, including GSH, labile iron levels, and ferroptosis regulators by Western blot, qRT-PCR, immunohistochemistry, and immunofluorescence. The level of malondialdehyde (MDA) and the fluorescence intensity of BODIPY probe indicated the level of lipid peroxidation. It was demonstrated that solute carrier family 7, member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were less expressed in renal biopsy samples from patients affected by DKD than in those from non-diabetic renal disease patients (NDRD), proving the ferroptosis of tubular epithelial cells in case of DKD. Furthermore, empagliflozin markedly decreased the ferroptosis impairment in DKD mice, as well as in HG model of HK-2cells. Our investigations showed the ability of empagliflozin to suppress ferroptosis was partially countered by AMP-activated protein kinase (AMPK) inhibitor, which led to a reduction of the nuclear translocation of the antioxidant transcription factor NFE2-related factor 2 (NRF2) and downregulation of target genes such as GPX4, ferritin heavy chain 1 (FTH1), and SLC7A11, while AMPK agonists were responsible for the enhancement of the protective effects of empagliflozin. Taken together, our findings showed that empagliflozin may prevent the development of ferroptosis by promoting the AMPK-mediated NRF2 activation pathway, providing important insights for possible novel treatment approaches for DKD.

External Validation of a Predictive Model of Non-Diabetic Renal Disease in Patients With Type 2 Diabetes Mellitus

External Validation of a Predictive Model of Non-Diabetic Renal Disease in Patients With Type 2 Diabetes Mellitus

MO611: Glycated Albumin Levels Predict The Type of Kidney Damage in Diabetic Patients

Abstract BACKGROUND AND AIMS Diabetes mellitus remains the most frequent cause of end-stage renal disease (ESRD) in developing countries. The main determinant of the onset of nephropathy in diabetes is hyperglycemia which brings to glycation of albumin and haemoglobin with higher concentration of AGEs (advanced glycation end products), finally leading to fibrosis, inflammation and albuminuria. Glycated albumin (GA) was introduced as an alternative to hemoglobin A1c (HbA1c) for glycemic control in the CKD population, with some advantages for diabetic patients with diabetic kidney disease (DKD), since it is not influenced by anemia and associated treatments and it is not affected by serum albumin levels. Although some evidences in literature demonstrated that GA is superior to HbA1c in assessing blood glucose control in DKD (Gan T et al. J Diabetes Complications. 2018); however, KDIGO Guidelines still recommend HbA1c, although underlying some limitations in the context of DKD, meaning that new markers are needed in order to monitor this class of diabetic patients. Kidney disease in diabetic patients can include different kind of renal damage ranging from real diabetic nephropathy (DN, with Kimmelstiel–Wilson lesions, glomerular basal membrane thickening, proliferation of mesangial matrix) to nondiabetic renal disease (NDRD), in the presence or absence of real DN, thus influencing prognosis and treatment. The purpose of the study was to evaluate the clinical utility of the GA dosage, alone or with other molecular and clinical markers as noninvasive biomarkers for the prediction of the progression and type of kidney damage in the diabetic patient. METHOD We enrolled 108 diabetic patients in follow-up at our center, 90 with a biopsy-proven diagnosis of kidney disease and 18 with no kidney dysfunction. Among the 90 patients, 51 had real diabetic nephropathy (DN) or mixed forms (DN + NDRD) and 39 had non-diabetic renal disease (NDRD). GA dosage was obtained by QuantILab® Glycated Albumin assay (Instrumentation Laboratory SpA, Milan, Italy). qPCR was used to evaluate urinary levels of miR27b-3p, a biomarker that predicts the kind of renal damage in diabetic patients and is related to kidney fibrosis (Conserva F et al. Sci Rep. 2019). Statistical analysis was performed using ‘SPSS Statistical Software.’ RESULTS We observed that GA values had a significantly different distribution among DN, NDRD and diabetic patients without renal dysfunction (P = 0.003); conversely, there was no statistical difference in HbA1c distribution although a trend was visible. In the entire cohort, only GA levels, but not HbA1c levels, were significantly correlated with fasting glucose (P = 0.001) and the duration of diabetes (P = .001). In the single classes, only in DN patients there was a significant correlation between GA and diabetes duration (P = .02) and GA and HbA1c (P = 0.01) but not in the NDRD class (P = 0.43). We then applied a multivariate logistic regression model to discriminate real DN and NDRD. We demonstrated that GA is the only significant predictor of real DN in a model corrected for sex, age and serum creatinine {P = 0.009; OR = 0.757–0.962; [95% confidence interval (CI)]}, whereas the same logistic regression model with HbA1c demonstrated no significance (P = 0.082). In the same cohort, we also evaluated miR-27b-3p expression levels, whose levels are correlated with renal fibrosis in DN, and we observed that there was a significant and direct correlation also with GA levels (P = 0.001), thus suggesting the possibility to integrate these biomarkers to predict the kind of renal damage in diabetic patients. CONCLUSION Our study described for the first time the role played by GA as a diagnostic marker in the identification of the different kind of renal damage in diabetic patients. All these evidences support the need to introduce GA as an index of glycemic control to be associated with other molecular markers, such as miRNAs, in order to noninvasively diagnose the kind of renal damage in diabetic patients.

Clinical Prediction Score for Diagnosing Non-Diabetic Renal Disease in Patients with Type 2 Diabetes Mellitus

Background: When non-diabetic kidney disease (NDKD) is suspected, biopsy proven is used for definite diagnosis. However, there are not always easily available and may lead to cause complications. A clinical prediction score may help selecting appropriate patients for kidney biopsy. Objective: To develop a clinical prediction score for distinguishing any type of NDKD (NDKD alone or coexisting NDKD and diabetic nephropathy [DN]) and DN alone. Materials and Methods: A retrospective cohort study was conducted in type 2 diabetes mellitus (T2DM) patients with atypical features of DN, who had kidney biopsy at Thammasat University Hospital between 2011 and 2019. The present study divided patients into NDKD alone, coexisting NDKD and DN, and DN alone, confirmed by pathological diagnoses. The authors developed a clinical prediction score by weighing coefficients of predictors in a multivariable logistic model. Internal validation was performed with bootstrapping. Results: The present study included 81 patients of which 28 (34%) had NDKD alone, 15 (18%) had coexisting NDKD and DN, and 38 (41%) had DN alone. Primary membranous nephropathy, primary focal segmental glomerulosclerosis (FSGS), and secondary FSGS were prevalent in any NDKD. Absence of diabetic retinopathy (DR) showed a significant association with any NDKD (adjusted OR 3.72; 95% CI 1.28 to 10.8; p=0.02). The prediction score, AUROC of 0.75 (95% CI 0.63 to 0.86), had four predictors, duration of DM of less than 10 years, eGFR of more than 30 mL/minute/1.73 m², HbA1c of less than 8%, and absence of DR. Higher scores were associated with higher probability of NDKD. Conclusion: The present study clinical prediction score appears to be a useful tool to determine NDKD probability. T2DM patients with atypical presentation of DN with lower scores (0 to 2) may defer kidney biopsy. Keywords: Non-diabetic kidney disease; clinical prediction score; kidney biopsy; type 2 diabetes mellitus

Spectrum of non-diabetic renal disease in patients with diabetes mellitus in a tertiary care hospital

Aim and Objectives: To analyse frequency and spectrum of non diabetic renal disease (NDRD) in type 2 diabetes patients and also determine the clinical markers associated with NDRD. Methodology: Single centre based prospective observational study carried out during the period from M a y 2016 to September 2019. Type 2 DM patients with atypical clinical renal disease who underwent renal biopsy to rule out NDRD at King George Hospital, Visakhapatnam were included in the study. Results: In the present study, the overall prevalence of NDRD with or without underlying DN in our study was 71.7%. The prevalence rates of isolated NDRD, NDRD with DN and isolated DN were 51.2%, 20.5%, and 28.2% respectively. Shorter duration of diabetes, absence of retinopathy, presence of active urine sediment are markers associated with NDRD in type 2 diabetics and are strong indicators for biopsy. Isolated DN group patients suffer significantly with hypertension compared to NDRD group. Isolated NDRD group patients had low HbA1c (

Manifestation of rs1888747 polymorphisms in the FRMD3 gene in diabetic kidney disease and diabetic retinopathy in type 2 diabetes patients

BackgroundFRMD3 polymorphisms has suggested that they could be an alternative test to differentiate diabetic nephropathy (DN) from nondiabetic renal disease (NDRD) in type 2 diabetes mellitus (DM) patients. This study was performed to investigate the relationship between the FRMD3 gene and clinical characteristics of DN.MethodsPatients who already had renal pathologic results were tested for FRMD3 polymorphisms. The subjects were classified into three groups; DN with diabetic retinopathy (DR), DN without DR, and DM with NDRD. FRMD3 polymorphisms were analyzed in each group.ResultsThe prevalence of GG, CG, and CC was 44.4%, 42.2%, and 13.3% respectively. There was no significant difference in clinical parameters, which consisted of disease duration, proteinuria, and complications in DN with or without DR and DM with NDRD. The G allele was mainly found in DN with DR patients (50.8%) whereas the C allele was found in DM with NDRD patients (43.5%) (p = 0.02). There was a significant association between the CC genotype in NDRD when compared to GG (p = 0.001). In addition, the C allele was 2.10-fold more often associated with NDRD than the G allele (p = 0.03). The CC genotype was correlated with risk for NDRD than the GG and GC genotypes, with odds ratios of 6.89 and 4.91, respectively (p = 0.02).ConclusionC allele presentation, especially homozygous CC, was associated with NDRD pathology in patients with overt proteinuria. Hence, kidney biopsy is suggested in those with the C allele or homozygous CC genotype, regardless of retinopathy manifestations.

A retrospective cohort study on the pathology and outcomes of type 2 diabetic patients with renal involvement.

To investigate the association of clinical and histological characteristics and the development of ESRD in T2DM patients with renal involvement. We conducted a retrospective analysis of clinical and pathologic data from T2DM patients who underwent renal biopsy (n = 120). The mean age, duration of diabetes, and eGFR were 50.9 ± 11.2years, 92.8 ± 41.3months, 55.1 ± 42.3mL/min/1.73 m2, respectively. Among these patients, 57 (47.5%) were diagnosed with diabetic nephropathy (DN), and 63 (52.5%) with non-diabetic renal disease (NDRD). The most common subtype of NDRD is membranous nephropathy. Compared with the NDRD group, the DN group had a longer duration of diabetes, worse renal function, and a higher proportion of diabetic retinopathy. Kaplan-Meier analysis showed that the 5-year renal survival rate of the DN group was only 41%, whereas that of the NDRD group was 84%. ESRD was defined as eGFR below 15mL/min/1.73 m2. After multivariate adjustment, the risk of ESRD in DN patients was 3.81 times higher than that in NDRD patients. According to Glomerular Class, the 5-year renal survival rate of type IIA, IIB, III, and IV in the DN group was 88, 56, 28, and 15%, respectively. Kaplan-Meier analysis showed that there was a significant difference in renal survival among different glomerular classes or different interstitial fibrosis and tubular atrophy (IFTA) scores. But Cox proportional hazards analysis indicated that only IFTA score (HR 2.75, 95% CI 1.37-5.51, P = 0.001), but not the glomerular class (HR 1.21, 95% CI 0.73-2.00, P = 0.465), could predict renal outcome when adjusting for multivariate. The prognosis of DN patients is significantly worse than that of NDRD patients. Compared with glomerular lesions, tubulointerstitial lesions were associated with higher risk for renal death in DN patients.

The Prevalence of Nondiabetic Renal Diseases in Patients with Diabetes Mellitus in the University Hospital of Ribeirão Preto, São Paulo.

Objective To evaluate the prevalence of nondiabetic renal diseases (NDRDs) in renal biopsies of patients with diabetes mellitus (DM) in the University Hospital of Ribeirão Preto, São Paulo. Research Design and Methods. We conducted a retrospective study including kidney biopsies performed in diabetic patients between 1987 and 2013. We evaluated 79 biopsies during this period. The primary variable was the prevalence of NDRD in patients with DM. The secondary variables were the presence of systemic arterial hypertension (SAH), hematuria, time since diagnosis of DM, serum creatinine, and proteinuria levels. The cases were divided into the following groups: isolated diabetic nephropathy (DN—group I), isolated nondiabetic renal diseases (NDRD—group II), associated NDRD/DN (group III), and associated NDRD+NDRD/DN (group IV). Results Most of the patients (58.22%) presented only alterations arising from DN. NDRDs were present in 41.77% of the patients. Membranous glomerulonephritis (30.3%) and IgA nephropathy (24.24%) were the most prevalent NDRDs. We found no differences between female and male patients with NDRD when assessing the secondary variables. A time since diagnosis of five years or less revealed a statistical difference (p = 0.0005) in the comparison between the isolated DN (group I) and the NDRD+NDRD/DN (group IV). The other secondary variables were not significant in the comparison of the groups. Conclusions We concluded that the prevalence of NDRD is 41.77%. Membranous glomerulonephritis was the most prevalent NDRD in our study. We also conclude that the probability of the presence of NDRD with or without concomitant DN is greater for patients who had biopsies with a time since diagnosis of five years or less. A time since diagnosis of ten years or more does not allow the exclusion of the presence of NDRD.

P1022HEMATURIA AND ABSENCE OF RETINOPATHY ARE NOT INDICATIVE OF NON -TYPE 2 DIABETES ASSOCIATED RENAL DISEASE IN PATIENTS WITH OTHERWISE TYPICAL DIABETIC KIDNEY DISEASE

Abstract Background and Aims Diabetic Nephropathy (DN) is usually a presumptive diagnosis based on clinical and biological evidences. However, Renal Biopsies (RB) may be performed when the suspicion of Non-Diabetic Renal Disease (NDRD) with potential specific treatment arises from atypical features mainly identified through studies focusing on the power of individual clinical and biological features to predict NDRD. We aimed to assess the actual value of RB indications (RBi) to discriminate NDRD from Type 2 Diabetes (T2D) Associated Renal Disease (T2D-ARD) such as DN and Hypertensive nephropathy which are frequently associated, seen in similar patients with high cardiovascular risk, lack for specific treatment and might be therefore be considered as “failure events” in the context of RB performed to diagnose NDRD with specific treatment. Method We conducted a retrospective multicenter study in four nephrology units and reviewed the charts of patients with T2D who underwent a first RB from 2006 to 2015. Clinical and biological characteristics, RBi and diagnoses were retrospectively collected from the patients’ medical charts. RBi were defined according to the sequence in Figure 1. As such, diabetic retinopathy may be absent in patients of all indication groups, conversely, patients in group 6 and 7 had stable proteinuria and renal function. Similarly, patients with monoclonal gammopathy were all included in group 1.We considered missing data regarding the absence/presence of Diabetic Retinopathy (DR) as meaningful, suggesting the data was unneeded to reach a decision of RBi. We performed univariate and multivariate logistic regression analyses to identify clinical or biological features associated with the diagnosis of NDRD. We also compared the number and percentage of actual NDRD diagnosed for each of the RBi. Results 464 first renal biopsies were performed in 464 patients during the study period. Two RB were excluded because the RBi could not be clearly identified through careful reviewing of the patients’ medical charts. Of the 462 remaining RB, 40% revealed NDRD. The most frequent were acute interstitial nephritis, IgA nephropathy and acute tubular necrosis (8.7%, 5.8% and 4.1% respectively). Patients with NDRD were more frequently &amp;gt;65yo (55 vs 44%), with serum creatinine (SCr) &amp;gt;250 µmol/l (52 vs 30%), hematuria (58 vs 36%), non-retrieved DR status (45 vs 17%), and less frequently with urinary-to-protein ratio (UPCR) &amp;gt;3g/g (33 vs 57%), HbA1c &amp;gt;7% (32 vs 50%) and duration of diabetes &amp;gt;5 years (52 vs 72%).Logistic regression analyses identified high SCr, UPCR, hematuria and low diabetes duration as predictive of NDRD. Surprisingly, missing RD status rather than absence of RD was predictive of NDRD. As expected NDRDs were frequent in patient with RBi 1 to 3 (53%, 40% and 21%), infrequent in patients with RBi 5 (7%) and totally absent from patients with RBi 6 and 7 despite their predictive value as regards with NDRD. Conclusion Our study confirms several well-known facts on the subject of renal biopsy in patients with T2D: 1) Renal biopsy is useful in selected patients with T2D and renal disease to diagnose NDRD with specific treatment. 2) Hematuria and short duration of diabetes are predictive of NDRD. On the other hand, our study suggests two novel and antidogmatic findings: 1) Assessing the presence of diabetic retinopathy is not required for RBi. 2) Hematuria is not indicative of NDRD in patients with otherwise typical diabetic kidney disease. Of course, our study is limited by its retrospective design precluding us of precisely defining what was considered rapid evolution of DFG or proteinuria emphasizing the need for prospective studies.

Risk factors for non-diabetic renal disease in diabetic patients.

BackgroundDiabetic 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.MethodsRetrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014.ResultsIn 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.ConclusionsThe 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.

Prevalence of Nondiabetic Renal Disease in Patients with Type 2 Diabetes Mellitus with Clinicopathological Correlation: A Study from a Tertiary Care Center of Assam, India.

Diabetes mellitus is the most common cause of chronic kidney disease worldwide. The prevalence of nondiabetic renal disease (NDRD) among patients with type 2 diabetes mellitus (T2DM) varies widely. This study aimed to evaluate the renal biopsies performed on type 2 diabetic patients for suspicion of NDRD and to correlate clinicopathological findings. All T2DM patients aged > 18 years were included in this study, who had renal biopsy performed for the following reasons: recent-onset nephrotic syndrome, unexplained rapid deterioration of renal function, proteinuria not accompanied by retinopathy, and unexplained hematuria. Renal biopsy was analyzed by light microscopy and immunofluorescence. Based on biopsy findings, the patients were grouped into three: (i) isolated NDRD, (ii) NDRD ± diabetic nephropathy (DN), and (iii) isolated DN. A total of 140 patients were enrolled in this study. Recent-onset nephrotic syndrome was the most common indication for biopsy, followed by the presence of active urine sediment. Forty-two percent of the patients had isolated DN, while NDRD was seen in 34% and DN ± NDRD in 24%. Focal segmental glomerulosclerosis (FSGS) and IgA nephropathy were the most common causes of isolated NDRD, while chronic tubulointerstitial nephritis (CTIN) was common in NDRD plus DN. Short duration of diabetes, absence of diabetic retinopathy, and lower glycated hemoglobin were predictive of NDRD. NDRD was seen in 58% of the patients with atypical presentations. FSGS and CTIN were common in NDRD diseases. Judicious use of biopsy in diabetic patients with atypical presentation may help in the diagnosis of NDRD.

Non-diabetic renal diseases in patients with diabetes mellitus clinicopathological correlation

Background and Aims:Non-diabetic renal diseases (NDRDs) form an important part of disease manifestations in patients with diabetes.Methods:This hospital-based prospective study was conducted to analyze incidence and spectrum of NDRDs in patients with diabetes with or without diabetic nephropathy (DN), effect of early specific interventions on outcome, and renal-retinal relationship in type 1 and type 2 diabetes mellitus with nephropathy. 44 Patients with T2DM with the clinical suspicion of NDRD were subjected to renal biopsy Renal biopsies were performed by using an automated biopsy gun. Tissue was processed for Light microscopy-LM and Immunofluorescence-IF. Electron Microscopy was done as and when required by reprocessing the tissue embedded in paraffin for LM. Biopsies were reported by one experienced renal pathologist.Results:Renal histopathology revealed that of 44 enrolled patients with clinically suspected NDRD, 61.4% had isolated NDRD, 13.6% had NDRD superimposed on DN, and 25% had isolated DN. The most common NDRDs were minimal change disease (19.2%) and DN + chronic pyelonephritis (33.3%) in patients with isolated NDRD, and NDRD superimposed on DN, respectively. In the DN group, no patient had proliferative diabetic retinopathy (PDR) or hypertensive retinopathy, 45.5% had nonproliferative diabetic retinopathy (NPDR) and 54.5% had no microangiopathy in retina. In the NDRD group, 9.1% each had PDR and hypertensive retinopathy, 36.4% had NPDR and 45.4% had no microangiopathy in retina. No patient in the DN group and 72.7% in the NDRD group received specific treatment. In hospital, dialysis support was provided to 27.3% and 21.2% of patients in the DN and NDRD groups, respectively. In the DN group, 72.7% of patients improved with conservative therapy, 18.2% were dependent on dialysis when discharged. One patient died during treatment. In the NDRD group, 78.8% showed recovery in the renal function and clinical improvement, 15.1% were dialysis dependent when discharged. Two patients died during treatment.Conclusion:Accurate diagnosis of underlying NDRD by kidney biopsy facilitates initiation of specific therapy, which may lead to clinical improvement in significant number of patients.

Design and validation of a scoring model for differential diagnosis of diabetic nephropathy and nondiabetic renal diseases in type 2 diabetic patients.

We aim to design a scoring model for differential diagnosis between diabetic nephropathy (DN) and nondiabetic renal disease (NDRD) in type 2 diabetic patients through a combination of clinical variables. A total of 170 patients with type 2 diabetes who underwent kidney biopsies were included and divided into three groups according to pathological findings: DN group (n = 46), MIX group (DN + NDRD, n = 54), NDRD group (n = 70). Clinical characteristics and laboratory data were collected and compared among groups. Variables with a significant statistical difference between DN and NDRD patients were analyzed by logistic regression to predict the presence of NDRD; then a scoring model was established based on the regression coefficient and further validated in an independent cohort of 67 patients prospectively. On biopsy, 72.9% of patients had NDRD, and the most common pathological type was membranous nephropathy. The established scoring model for predicting NDRD included five predictors: age, systolic blood pressure, hemoglobin, duration of diabetes, and absence of diabetic retinopathy. The model demonstrated good discrimination and calibration (area under curve [AUC] 0.863, 95% CI, 0.800-0.925; Hosmer-Lemeshow [H-L] P = .062). Furthermore, high prediction accuracy (AUC = 0.900; 95% CI, 0.815-0.985) in the validation cohort proved the stability of the model. We present a simple, robust scoring model for predicting the presence of NDRD with high accuracy (0.85) for the first time. This decision support tool provides a noninvasive method for differential diagnosis of DN and NDRD, which may help clinicians assess the risk-benefit ratio of kidney biopsy for type 2 diabetic patients with renal impairment.

Predictors and histopathological characteristics of non-diabetic renal disorders in diabetes: a look from the tubulointerstitial point of view.

Prevalence and characteristics of non-diabetic renal diseases (NDRD) in patients with type 2 diabetes mellitus is different between populations, and seems to be largely dependent on biopsy policies. To investigate clinical clues for NDRD in patients with type 2 diabetes mellitus and to analyse renal prognosis of patients based on pathological diagnosis. We retrospectively searched medical records of 115 patients with type 2 diabetes who underwent a renal biopsy between 2004 and 2018. Patients were divided into three groups as diabetic nephropathy (DN), NDRD + DN or NDRD based on histopathological examination. Thirty-six (31.3%) patients had DN, 33 (28.7%) had DN + NDRD and 46 (40%) had NDRD. The absence of diabetic retinopathy, recent onset of diabetes, abnormal disease chronology, and blood haemoglobin was associated with the presence of NDRD in univariate analysis. Abnormal disease chronology which was defined as the presence of acute proteinuria and/or acute kidney injury that are unexpected to be related to evolution of diabetic nepropathy (odds ratio 4.65, 95% confidence interval 1.44-15.00; P = 0.010) and absence of diabetic retinopathy (odds ratio 3.44, 95% confidence interval 1.32-8.98; P = 0.012) were independently associated with the presence of NDRD in multivariate analysis. Focal segmental glomerulosclerosis was the most frequent type of NDRD. Diseases that affect tubulointerstitial area were more prevalent in the DN + NDRD group compared to the NDRD group (P = 0.001). Renal survival, which was defined as evolution to end-stage renal disease, was 59.5 ± 14.4 months, 93.7 ± 11.7 months and 87.2 ± 2.6 months for DN, DN + NDRD and NDRD groups, respectively (P = 0.005). Renal biopsy is essential in certain clinical conditions as diagnosis of NDRD is vital for favourable renal survival. DN may facilitate superimposed tubular injury in the presence of toxic insults.

A Differential Diagnosis Model For Diabetic Nephropathy And Non-Diabetic Renal Disease In Patients With Type 2 Diabetes Complicated With Chronic Kidney Disease.

PurposeDifferentiating between diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) is difficult and inefficient. The aim of the present study was to create a model for the differential diagnosis of DN and NDRD in patients with type 2 diabetes mellitus (T2DM).Patients and methodsWe consecutively screened 213 patients with T2DM complicated with chronic kidney disease, who underwent renal biopsy at The First Affiliated Hospital of Guangxi Medical University (Nanning, China) between 2011 and 2017. According to the pathological results derived from the renal biopsy, the patients were divided into three groups (74, 130, and nine in the DN, NDRD, and NDRD superimposed with DN group, respectively). Clinical and laboratory data were compared and a diagnostic model was developed based on the following logistic regression model: logit(P)=n{beta _0}n+n{beta _1}{X_1}n+n{beta _2}{X_2}n+ … +n{beta _m}{X_m}n.ResultsWe observed a high incidence of NDRD (61.0% of all patients), including various pathological types; the most common type was idiopathic membranous nephropathy. By comparing clinical variables, we identified a number of differences between DN and NDRD. Logistic regression analyses showed that the following variables were statistically significant: the absence of diabetic retinopathy (DR), proteinuria within the non-nephrotic range, the absence of anemia and an estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2. We subsequently constructed a diagnostic model for predicting NDRD, as follows: PNDRD=1/[1+exp(−17.382–3.339×DR−1.274×Proteinuria−2.217×Anemia-1.853×eGFR−0.993×DM+20.892Bp)]. PNDRD refers to the probability of a diagnosis of NDRD (a PNDRD≥0.5 predicts NDRD while a PNDRD<0.5 predicts DN); while DM refers to the duration of diabetes. This model had a sensitivity of 95.4%, a specificity of 83.8%, and the area under the receiver operating characteristic curve was 0.925.ConclusionOur diagnostic model may facilitate the clinical differentiation of DN and NDRD, and assist physicians in developing more effective and rational criteria for kidney biopsy in patients with T2DM complicated with chronic kidney disease.