Non-diabetic Renal Disease Research Articles

Clinical correlates and pathology of non-diabetic renal disease in diabetes mellitus

Objectives: Early identification and differentiation of patients with non-diabetic renal disease (NDRD) from diabetic nephropathy (DN) or those with NDRD superimposed on DN improves the prognosis and reduces associated morbidity. The objectives of the study were to compare the clinical profile, nature of renal involvement, and etiopathogenesis (renal biopsy) of patients with isolated NDRD and NDRD superimposed on DN. Materials and Methods: It is a descriptive study in patients with T2D and renal involvement suggestive of non-diabetic etiology further evaluated with renal biopsy and grouped as NDRD alone or NDRD with DN. Results: Of the total 50, 66% were male, the mean age was 55.57 ± 12.28 years, and all were proteinuric. Overall, isolated NDRD and NDRD superimposed on DN were observed in 64% and 36% of patients, respectively. Diabetic retinopathy was absent in 82% of cases. The most common finding in isolated NDRD was membranous nephropathy, followed by immunoglobulin A (IgA) nephropathy and rapid progression of glomerular nephritis (RPGN). At the same time, in the NDRD and DN group, maximum patients displayed IgA nephropathy followed by acute tubular necrosis and RPGN. The incidence of atypical features of renal disease was almost twice as high in the isolated NDRD group than in the group with both NDRD + DN. Conclusion: NDRDs are highly prevalent, and DN may superimpose these. Recognizing NDRD solely on the basis of clinical indicators is challenging. Therefore, histopathological analysis seems essential to accurately diagnose NDRD in diabetic patients to reduce the probability of missed NDRD diagnosis and initiate prompt treatment.

The role of kidney biopsy in deciphering diabetic versus non-diabetic origin of kidney disease among patients with type 2 diabetes mellitus and nephrotic range proteinuria: A retrospective study

BackgroundDiabetes mellitus (DM) is tightly associated with the increased prevalence of diabetic kidney disease (DKD). Nonetheless, severe renal function impairment and/or nephrotic range-proteinuria could also result from non-diabetic renal disease (non-DRD) among patients with DM. The ‘Gold standard’ for the differential diagnosis between DKD and non-DRD is kidney biopsy, although no real consensus exists. Thus, this study intends to associate the clinical and biochemical profile of patients with DM and renal disease with the histopathological data of kidney biopsy.In addition, we aimed to evaluate the role of kidney biopsy, especially when other causes, other than DM, are highly suspected among patients with DM and kidney disease. MethodsThirty two patients with T2DM and nephrotic range levels of proteinuria or with co-existing factors pointing towards a non-diabetic origin of kidney disease were studied, retrospectively. All 32 patients underwent kidney biopsy and were classified according to histopathological findings into 3 groups: a) isolated diabetic kidney disease (DKD), b) non-diabetic kidney disease (NDKD) and c) mixed kidney disease (MKD). ResultsFifteen out of the 32 patients had findings of an isolated DKD, while 17 out of 32 patients suffered from NDKD (13 patients) or MKD (4 patients). DKD patients were younger (p = 0.016) and had a higher HbA1c value (p = 0.069, borderline statistical significance), while the NDKD patients had significantly shorter disease duration (p = 0.04). Furthermore, the incidence of diabetic retinopathy (DR) was lower among the NDKD patients (p < 0.001), who had also significantly less interstitial fibrosis (p = 0.02). Finally, the presence of DR, higher levels of interstitial fibrosis and longer T2DM duration were recognized as factors, which were positively associated with DKD. ConclusionThis study advocates the usefulness of kidney biopsy in patients with T2DM and nephrotic range levels of proteinuria, especially when DR is absent and shorter disease duration is observed.

COVID-19 epidemic investigation study of a follow-up cohort of patients with diabetic kidney disease.

The impact of coronavirus disease 2019 (COVID-19) on diabetic kidney disease (DKD) patients in China is not fully understood. This study aimed to investigate infection status in a DKD cohort post-renal biopsy and analyze vaccination and infection rates, as well as symptom severity, across various renal pathologies in DKD patients. This epidemiological survey, centered on COVID-19, employed a Chinese DKD and renal puncture follow-up cohort. A customized questionnaire enabled standardized data gathering. It collected data on clinical characteristics, vaccination and infection statuses, and diverse pathological types. The study analyzed the relationship between vaccination and infection statuses across various pathological types, evaluating characteristics and treatment outcomes in patients with infections. In total, 437 patients with DKD from 26 Chinese provinces were followed up for a median of 44.6 ± 20 months. COVID-19 infection, vaccination, and novel coronavirus pneumonia (NCP) rates were 73.68%, 59.3%, and 6.63%, respectively. Ten patients with NCP had severe pneumonia or died of COVID-19. Renal pathology revealed that 167 (38.22%) patients had diabetic nephropathy (DN), 171 (39.13%) had non-diabetic renal disease (NDRD), and 99 had DN and NDRD (22.65%). The DN group had the lowest vaccination (54.5%), highest all-cause mortality (3.6%), and highest endpoint rates (34.10%). Compared to patients who were not vaccinated pre-infection (117 cases), vaccinated patients (198 cases) had reduced NCP (6.6% vs. 13.7%), severity (1.0% vs. 3.4%), and endpoint (9.10% vs. 31.60%) rates. Vaccination can prevent infection and diminish COVID-19 severity in patients with DKD; therefore, increasing vaccination rates is particularly important. ClinicalTrails.gov, NCT05888909.

Risk evaluation for diabetic retinopathy in Chinese renal-biopsied type 2 diabetes mellitus patients.

To investigate diabetic retinopathy (DR) prevalence in Chinese renal-biopsied type 2 diabetes mellitus (T2DM) patients with kidney dysfunction, and to further evaluate its relationship with diabetic nephropathy (DN) incidence and the risk factors for DR development in this population. A total of 84 renal-biopsied T2DM patients were included. Fundus and imaging examinations were employed for DR diagnosis. Demographic information and clinical measures along with renal histopathology were analyzed for comparisons between the DR and non-DR groups. Risk factors on DR development were analyzed with multiple logistic regression. DR prevalence was 50% in total. The incidences of DN, non-diabetic renal disease (NDRD) and mixed-type pathology were 47.6%, 19.0% and 33.3% in the DR group respectively, while 11.9%, 83.3% and 4.8% in the non-DR group. Systolic blood pressure, ratio of urinary albumin to creatine ratio, urinary albumin, 24-hours urinary protein, the incidence and severity of DN histopathology were found statistically increased in the DR group. Multiple logistic regression analysis showed histopathological DN incidence significantly increased the risk of DR development [odds ratio (OR)=21.664, 95% confidential interval (CI) 5.588 to 83.991, P<0.001 for DN, and OR=45.475, 95%CI 6.949 to 297.611, P<0.001 for mixed-type, respectively, in reference to NDRD)], wherein DN severity positively correlated. Renal histopathological evidence indicates DN incidence and severity increases the risk of DR development in Chinese T2DM patients inexperienced of regular fundus examinations.

Correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 diabetic nephropathy.

Diabetic nephropathy (DN) and diabetic retinopathy (DR) are common microvascular complications of diabetes. The purpose of this study was to investigate the correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 DN and to determine the capacity of retinal vascular geometric parameters in differentiating DN from non-diabetic renal disease (NDRD). The study participants were adult patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease who underwent a renal biopsy. Univariate and multivariable regression analyses were performed to evaluate associations between retinal vessel geometry parameters and pathologically diagnosed DN. Multivariate binary logistic regression analyses were performed to establish a differential diagnostic model for DN. In total, 403 patients were examined in this cross-sectional study, including 152 (37.7%) with DN, 157 (39.0%) with NDRD and 94 (23.3%) with DN combined with NDRD. After univariate logistic regression, total vessel fractal dimension, arteriolar fractal dimension and venular fractal dimension were all found to be associated with DN. In multivariate analyses adjusting for age, sex, blood pressure, diabetes, DR and other factors, smaller retinal vascular fractal dimensions were significantly associated with DN (P<.05). We developed a differential diagnostic model for DN combining traditional clinical indicators and retinal vascular geometric parameters. The area under the curve of the model established by multivariate logistic regression was 0.930. Retinal vessel fractal dimension is of great significance for the rapid and non-invasive differentiation of DN. Incorporating retinal vessel fractal dimension into the diagnostic model for DN and NDRD can improve the diagnostic efficiency.

Sodium glucose cotransporter-2 inhibitors and heart disease: Current perspectives.

Sodium glucose cotransporter-2 inhibitors (SGLT-2i) are antidiabetic medications with remarkable cardiovascular (CV) benefits proven by multiple randomised controlled trials and real-world data. These drugs are also useful in the prevention of CV disease (CVD) in patients with diabetes mellitus (DM). Although DM as such is a huge risk factor for CVD, the CV benefits of SGLT-2i are not just because of antidiabetic effects. These molecules have proven beneficial roles in prevention and management of nondiabetic CVD and renal disease as well. There are various molecular mechanisms for the organ protective effects of SGLT-2i which are still being elucidated. Proper understanding of the role of SGLT-2i in prevention and management of CVD is important not only for the cardiologists but also for other specialists caring for various illnesses which can directly or indirectly impact care of heart diseases. This clinical review compiles the current evidence on the rational use of SGLT-2i in clinical practice.

#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.

#2660 WWP2-induced pericytes to myofibroblast transition contributes to the progression of fibrosis in CKD in diabetes

Abstract Background and Aims CKD in diabetes can be characterized by different clinical and histological phenotypes, associated to different molecular pathways specifically involved in the progression of kidney disease. CKD in diabetes includes different phenotypes, commonly classified according to Mazzucco et al (PMID:11920336) as diabetic Nephropathy (DN), non-diabetic renal disease (NDRD) and mixed forms (DN+NDRD). Among these, DN represents the primary cause of end stage renal disease (ESRD) and our group demonstrated that renal damage in DN is characterized by a specific molecular feature, represented by the activation of lysine63 (K63)-ubiquitination (Ub) pathway. In particular, we demonstrated that accumulation of K63-Ub proteins is involved in the progression of renal fibrosis (PMID: 27881486). WWP2 is an E3 ubiquitin-protein ligase that modulates myofibroblast pro-fibrotic activation in cardiac fibrosis (PMID: 31399586), however its specific role in kidney fibrosis in diabetes and its subsequent involvement in K63-Ub pathway has not been described so far. Thus aim of this study was to evaluate the involvement of WWP2 in the progression of kidney fibrosis in diabetes and its involvement in K63-Ub pathway. Method WWP2, K-63Ub, alpha-sma and PDGFbeta-receptor expression were evaluated in: i) 22 kidney biopsies from patients with a biopsy proven diagnosis of DN (n = 11), NDRD (n = 6) and CKD without diabetes (n = 5), by immunohistochemistry and immunofluorescence; ii) streptozotocin (STZ)-treated DBA/2J mice, a model of human DN, in the presence or absence of a specific inhibitor of K63Ub (NSC697923) by immunohistochemistry (n = 3 for each group); iii) in HK2 tubular cells, EAHY926 endothelial cells and in human-derived pericytes under hyperglycemic conditions by western blotting and qPCR. Results Immunohistochemistry showed that WWP2 was expressed both in CKD and in DN patients’ biopsies when compared to patients with NDRD (p &amp;lt; 0.05 and p &amp;lt; 0.01 respectively), both at tubular, glomerular and in the vascular compartment. Immunofluorescence confirmed that WWP2 increased expression in DN patients compared to NDRD, was associated to accumulation of K63Ub proteins in the tubular compartment as well as in the vascular compartment in particular in pericytes, cells that envelop the surface of vessels and have been described as the major source of scar-forming myofibroblasts in CKD (PMID: 19008372). The involvement of WWP2 in the K63-Ub pathway was confirmed in vivo in DBA2J diabetic mice in which the specific inhibition by NSC697923 of the K63Ub pathway, significantly reduced WWP2 expression in kidney tissues from diabetic mice (p &amp;lt; 0.05). These results were confirmed in vitro where specific inhibition of K63Ub pathway by NSC697923 significantly reduced hyperglycaemia-induced WWP2 expression in HK2 cells by western blotting and qPCR (p &amp;lt; 0.01). Hyperglycaemic conditions did not influence WWP2 expression in EAHY926 endothelial cells (p = n.s.). Conversely, using qPCR, in pericytes we observed an hyperglycemia-induced expression of both WWP2 levels (RR&amp;gt;2) and alpha-sma levels (RR&amp;gt;3) at different time points. Moreover, western blotting showed that hyperglycemia also induced a decrease of PDGF-beta-receptor marker of pericytes, thus suggesting their transition to myofibroblasts. Conclusion These findings demonstrate the influence of WWP2 on the k63-Ub pathway thus driving fibrogenesis in DN patients, in particular through pericyte to myofibroblast transition. WWP2 could represent a potential novel target for therapeutic intervention in the treatment of chronic kidney disease in diabetes.

#2265 The challenge of renal biopsy in diabetic patients: evaluation of a single center large cohort from North-West Italy

Abstract Background and Aims Diabetic kidney disease is one of the most severe long-term complications of diabetes. Currently, the international guidelines suggest diagnosis of diabetic nephropathy to be achieved on a clinical ground only. However, in the heterogeneous cluster of different conditions putatively co-existing with diabetes, renal biopsy is a unique tool for an accurate diagnosis and a guide for patient management. The aim of the study was to retrospectively analyze monocentric case history of kidney biopsies performed in diabetic patients over a period of 10 years. Patient's data were collected both at the time of histological examination and during follow-up. Method Data of renal biopsies (RB) performed in patients with diabetes mellitus from 1st January 2014 to 31th July 2023, were collected. Patient identification was performed by reviewing clinical histories and histopathological charts. Data on the indication for RB were collected from the medical report of the hospitalisation when the procedure was performed or from the visit when the indication was given. Atypical features were categorized according to an adaptation of the 2007 KDOQI guidelines for diabetes and chronic kidney disease. The significance of baseline differences was determined by the chi-squared test, Fisher's exact test or the unpaired t-test, as appropriate. Significance of univariate analysis were confirmed through the use of multivariate analysis. Correlation analysis, linear regression and Cox regression were also performed. A two-sided P-value &amp;lt;0.05 was statistically significant. All statistical analyses were performed using SPSS version 26.0 (IBM, Armonk, NY, USA). Results Among 1990 patients (pts) who underwent kidney biopsy during the study period, 297 had type 1 or type 2 DM (14.9%) and were therefore included in the study, regardless of diagnostic suspicion and histological findings. Histological examination revealed diabetic nephropathy (DN) in 112 cases (group 1), DN associated with another kidney disease in 56 cases (group 2) and nondiabetic renal diseases alone in the remaining 129 cases (62%) (group 3). In group 2 the kidney disease most frequently associated with DN was focal and segmental glomerulosclerosis, FSGS (24/56 pts) followed by IgA nephropathy, IgAN (14/56 pts). In this population the histological examination led to specific therapeutic indications in 22 patients. In group 3 the most frequently observed kidney disease was FSGS (37/112 pts) followed by ANCA-vasculitis (14/112 pts), membranous nephropathy (14/112 pts) and IgAN (10/112). In this population, histological examination led to a specific therapeutic indication in 67 pts. To determine predictors for histopathological diagnosis of DKD, we ran a logistic regression model. The covariates used in this model were the duration of diabetes, presence of retinopathy, hypertension, serum creatinine values, eGFR values and 24-hours proteinuria. None of them was found to be statistically significant. It should also be noted that 47 out of 112 pts (42%) with diabetic nephropathy had no retinopathy. In contrast, 9 pts (7%) with histological evidence of NDRD had diabetic retinopathy. 215 out of 297 pts had a follow-up of at least 6 months. During a mean follow up of 41.6±31.8 months, 53 pts (24 in group 1, 15 in group 2 and 14 in group 3) reached end stage kidney disease (16.5 months). In our population the presence of DN associated with another biopsy-proven nephropathy was especially prevalent. Having double nephropathy conferred a relative risk-RR for dialysis of 1.8089 (95% CI 1.0094 to 3.2415, P = .0464). Conclusion To our knowledge this is the largest cohorts of diabetic patients receiving renal biopsy even reported in a Western country. Our data proved kidney biopsy not to be an academic exercise in diabetic pts. Clinical and laboratory features do not predict histologic findings. Renal biopsy allowed the identification of unsuspecting nondiabetic kidney injuries and double nephropathies, which could be susceptible to different outcomes, and paved the pathway for treatment of potentially manageable histological changes.

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.

Screening candidate diagnostic biomarkers for diabetic kidney disease.

There are big differences in treatments and prognosis between diabetic kidney disease (DKD) and non-diabetic renal disease (NDRD). However, DKD patients couldn't be diagnosed early due to lack of special biomarkers. Urine is an ideal non-invasive sample for screening DKD biomarkers. This study aims to explore DKD special biomarkers by urinary proteomics. According to the result of renal biopsy, 142 type 2 diabetes mellitus (T2DM) patients were divided into 2 groups: DKD (n = 83) and NDRD (n = 59). Ten patients were selected from each group to define urinary protein profiles by label-free quantitative proteomics. The candidate proteins were further verifyied by parallel reaction monitoring (PRM) methods (n = 40). Proteins which perform the same trend both in PRM and proteomics were verified by enzyme-linked immunosorbent assays (ELISA) with expanding the sample size (n = 82). The area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of diagnostic biomarkers. We identified 417 peptides in urinary proteins showing significant difference between DKD and NDRD. PRM verification identified C7, SERPINA4, IGHG1, SEMG2, PGLS, GGT1, CDH2, CDH1 was consistent with the proteomic results and p < 0.05. Three potential biomarkers for DKD, C7, SERPINA4, and gGT1, were verified by ELISA. The combinatied SERPINA4/Ucr and gGT1/Ucr (AUC = 0.758, p = 0.001) displayed higher diagnostic efficiency than C7/Ucr (AUC = 0.632, p = 0.048), SERPINA4/Ucr (AUC = 0.661, p = 0.032), and gGT1/Ucr (AUC = 0.661, p = 0.029) respectively. The combined index SERPINA4/Ucr and gGT1/Ucr can be considered as candidate biomarkers for diabetic nephropathy after adjusting by urine creatinine.

Comparative analysis of hemodialysis and peritoneal dialysis on the risk of new onset diabetes mellitus

BackgroundDiabetes mellitus is a significant risk factor for cardiovascular events and mortality in dialysis patients. The impact of different dialysis modalities on the risk of new onset diabetes mellitus (NODM) remains a subject of debate. Previous studies did not adequately account for critical confounding factors such as pre-dialysis glycemic status, medication use, and nutritional status, which may influence the association between dialysis modality and NODM risk. MethodsWe conducted a retrospective cohort study of 1426 non-diabetic end-stage renal disease (ESRD) patients who underwent either hemodialysis (HD) or peritoneal dialysis (PD) at a single medical center. We used different statistical methods, adjusting for potential confounding factors, and accounted for competing risk of death. ResultsOver 12 years, 331 patients (23 %) developed NODM. After adjusting for potential confounding factors and mortality, PD patients had a significantly higher risk of NODM compared to HD patients (adjusted HR 1.52, p = 0.001). A propensity-matched cohort sensitivity analysis yielded similar results. Among patients with prediabetes, those receiving PD had a 2.93 times higher risk of developing NODM than those receiving HD (p for interaction <0.001), whereas no significant difference was observed among euglycemic patients. NODM was also associated with a 1.78 times increased risk of major cardiovascular events. ConclusionOur study provides evidence that PD treatment may increase the risk of NODM in ESRD patients, particularly among those with preexisting prediabetes. These findings highlight the importance of personalized treatment approaches, and nephrologists should consider prediabetes when choosing the dialysis modality for their patients.

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.

Should we enlarge the indication for kidney biopsy in patients with diabetes? The pro part.

Diabetic nephropathy (DN) and non-diabetic renal diseases (NDRD) represent intricate challenges in diagnosis and treatment within the context of the global diabetes epidemic. As the prevalence of diabetes continues to escalate, effective management of renal complications becomes paramount. Recent advancements in comprehending the multifaceted nature of renal damage, fueled by insights from histopathological investigations, offer unprecedented prospects for refining diagnostic strategies and customizing therapeutic interventions. Renal biopsies have emerged as indispensable tools for unraveling the diverse phenotypes of renal damage in diabetes. The pioneering study by Mazzucco identified three classes of renal damage in type 2 diabetes patients: classical diabetic glomerulosclerosis (DN), vascular and ischemic glomerular changes (NDRD), and other glomerulonephritides in the presence (DN+NDRD, mixed forms) or absence of DN (NDRD). The prevalence of these classes varies widely in published studies, influenced by factors such as ethnicity, geography and selection criteria for renal biopsy. Moreover, the international Renal Pathology Society consensus classification system has stratified the classical diabetic nephropathy into progressive categories of renal impairment, a breakthrough that aids in prognostication. Histopathological scrutiny, particularly the intricate correlation between glomerular and tubulointerstitial lesions, contributes profoundly to enhancing our grasp of the phenotype's heterogeneity. This amplified comprehension holds the potential to steer personalized treatment strategies. Cutting-edge interventions, encompassing sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and anti-endothelin receptor agents, are broadening the arsenal against renal injury in diabetes. When combined with the profound insights garnered from histopathological, omics, imaging and clinical data, these therapeutic avenues promise a transformative shift towards precision-driven care paradigms. Collaborative efforts uniting researchers, clinicians and patients are indispensable for propelling our knowledge of diabetic renal damage and ameliorating patient outcomes. The fusion of histopathological, omics and imaging findings into clinical decision-making harbors the potential to customize interventions and optimize care for individuals grappling with diabetes-associated renal complications. Furthermore, groundbreaking initiatives like the iBeat Study within the BEAt-DKD (Biomarker Enterprise to Attack Diabetic Kidney Disease) project (https://www.beat-dkd.eu/), elucidating distinct phenotypes of renal damage within diabetes, underscore the imperative necessity of integrating histopathological data into the broader framework of diabetic renal management.

Prevalence and Clinicopathological Characteristics of NDRD in Type 2 DM Patients

The prevalence of non-diabetic renal disease (NDRD) in type 2 diabetes mellitus (DM) varies depending on selection criteria and populations studied. Renal biopsies are not routinely performed in diabetic patients, but are indicated when NDRD is suspected. This study evaluated kidney biopsy histopathology and its correlation with clinical and biochemical parameters. Patients with type 2 DM who underwent renal biopsy for suspected NDRD from January 2015 to May 2023 were selected. Data analysis included clinical, laboratory, and histopathology findings. Patients were grouped as follows: Group I (pure diabetic nephropathy [DN]), Group II (NDRD with underlying DN), and Group III (pure NDRD). 41 biopsies were performed on type 2 DM patients. Mean age: 48.07±11.9 years, mean diabetes duration: 8.23±7.4 years, mean proteinuria: 11.37±8.0 mg/mmol, and mean creatinine: 2.19±2.05 mg/dl. 46.3% were hypertensives, 46.34% had diabetic retinopathy and 34.14% had hematuria. Among the studied group, 12 patients (29.26%) had pure DN, 10 patients (24.39%) had NDRD with underlying DN, and 19 patients (46.34%) had pure NDRD. The most common NDRD findings were membranous nephropathy 5 cases (26.31%) and focal segmental glomerulosclerosis 4 cases (21.05%). This study found a 46.34% incidence of NDRD in diabetic patients. NDRD should be suspected in atypical diabetic presentations, as early diagnosis and treatment may slow kidney disease progression.

Renal biopsy pattern in diabetes mellitus patients and their correlation with clinical parameters

Background. Diabetic nephropathy is a condition marked by persistent proteinuria, hypertension, and a progressive loss of renal function. End-stage kidney disease needing continuous renal replacement treatment is now primarily caused by diabetes. According to Kimmelstiel and Wilson, the hallmark lesion of diabetic nephropathy is nodular glomerulosclerosis. Diabetic nephropathy or Nondiabetic renal disease, or the coexistence of both can be seen in renal histopathology and in differentiating between these diagnostic groups can have an impact on patient care and prognosis.Patients and Methods. Total of 21 cases of Diabetic nephropathy were included in the study. Clinical details and laboratory parameters like diastolic blood pressure, creatinine level, 24 hrs urinary protein level and HbA1C% were recorded in pretested performa in all cases. The biopsy specimens were stained with hematoxylin &amp; eosin and special stains.Results. Among the total DM cases only 21 patients have done renal biopsy, 11 cases (52.3 %) showed KW lesion (Class III) while 06 cases (28.5 %) showed diffuse diabetic glomerulosclerosis (Class IV). The remaining 04 cases (19 %) showed a mild increase in mesangial matrix and slight thickening of glomerular basement membrane (Class II). When compared with clinical parameters, they were more raised in Nodular diabetic glomerulosclerosis type (Class III) lesion as compared to diffuse diabetic glomerulosclerosis.Conclusion. Nodular diabetic glomerulosclerosis was the most common lesion in renal biopsy of type II diabetes mellitus patients. This KW lesion is responsible for more severe clinical and biochemical renal abnormality in most patients with type II diabetes mellitus.

Incidence, Histopathological Pattern, and Predictors of Non-Diabetic Renal Disease in Type 2 Diabetes Mellitus: A Single-Center Prospective Observational Study

Patients with type 2 diabetes mellitus (T2DM) may have renal involvement because of isolated diabetic nephropathy (DN), isolated non-diabetic renal disease (NDRD), or mixed lesions (DN combined with NDRD). This study was conducted to find out incidence, histopathological pattern, and clinical predictors of NDRD in the Kashmiri population. This is a single-center prospective observational study conducted from August 2015 to July 2017. Patients with T2DM presenting with atypical clinical features of renal involvement underwent kidney biopsy. A total of 33 patients were included. Isolated NDRD was found in 16/33 (48.5%) patients, isolated DN was discovered in 10/33 (30.3%), and mixed lesions in 7/33 (21.2%) patients. NDRD with or without DN was present in 23/33 (69.7%) patients. Overall, the most common renal histopathological lesion in NDRD was immunoglobulin A (IgA) nephropathy present in 7/23 (30.4%) patients. In mixed lesions, FSGS and TMA were the most common renal lesions present in 2/7 (28.57%) patients. The mean duration of diabetes in NDRD and isolated DN groups was 4.4±3.6 and 7.0±2.9 years, respectively (P = 0.04). NDRD was present in 21/23 (91.3%) patients without diabetic retinopathy (P = 0.016). Our data demonstrated that more than half of the patients with T2DM with atypical features had NDRD upon renal biopsy. The absence of diabetic retinopathy and a shorter duration of diabetes were indicators of NDRD. IgA nephropathy was the most prevalent renal pathology. Clinicians must consider kidney biopsy liberally, especially in patients with unclear etiology of a kidney disease. Patients with type 2 diabetes mellitus (T2DM) may have renal involvement because of isolated diabetic nephropathy (DN), isolated non-diabetic renal disease (NDRD), or mixed lesions (DN combined with NDRD). This study was conducted to find out incidence, histopathological pattern, and clinical predictors of NDRD in the Kashmiri population. This is a single-center prospective observational study conducted from August 2015 to July 2017. Patients with T2DM presenting with atypical clinical features of renal involvement underwent kidney biopsy. A total of 33 patients were included. Isolated NDRD was found in 16/33 (48.5%) patients, isolated DN was discovered in 10/33 (30.3%), and mixed lesions in 7/33 (21.2%) patients. NDRD with or without DN was present in 23/33 (69.7%) patients. Overall, the most common renal histopathological lesion in NDRD was immunoglobulin A (IgA) nephropathy present in 7/23 (30.4%) patients. In mixed lesions, FSGS and TMA were the most common renal lesions present in 2/7 (28.57%) patients. The mean duration of diabetes in NDRD and isolated DN groups was 4.4±3.6 and 7.0±2.9 years, respectively (P = 0.04). NDRD was present in 21/23 (91.3%) patients without diabetic retinopathy (P = 0.016). Our data demonstrated that more than half of the patients with T2DM with atypical features had NDRD upon renal biopsy. The absence of diabetic retinopathy and a shorter duration of diabetes were indicators of NDRD. IgA nephropathy was the most prevalent renal pathology. Clinicians must consider kidney biopsy liberally, especially in patients with unclear etiology of a kidney disease.

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.

#6834 PREVALENCE, ETIOLOGY AND CLINICAL CHARACTERISTICS OF BIOPSY PROVEN NON-DIABETIC RENAL DISEASE: 10 YEARS OF BIOPSES IN DIABETIC PATIENTS

Abstract Background and Aims Diabetic nephropathy (DN) is the major cause of kidney disease in diabetic patients. However, a significant proportion of diabetic patients may actually have nondiabetic renal disease (NDRD). Therefore, it is important to identify patients who can benefit from a renal biopsy in order to establish the correct diagnosis. Our study aims to determine the prevalence and etiology of biopsy proven NDRD and to explore the clinical differences encountered in the diabetic patient with NDRD. Method Retrospective study of the medical records of all diabetic patients who underwent a renal biopsy due to suspicion of NDRD from January 2012 to December 2022 at Nephrology department Collected data comprised demographic information, indication and result of renal biopsy, lab results (serum creatinine, Hb1Ac, proteinuria, albuminemia, hematuria, presence of active urinary sediment and presence of auto antibodies) and disease's characteristics (duration of diabetes, presence of diabetic retinopathy). Categorical variables are presented as frequencies and percentages, continuous variables as means and standard deviations, or medians and interquartile ranges (IQR) for variables with skewed distributions. A p-value&amp;lt;0.05 was considered statistically significant. Statistical analysis was performed using SPSS version 28.1 for Mac OS X. Results 57 patients, 33.3% (n=19) were females, the medium age was 64.9 $\langle {{\rm{italic}}} \rangle \pm \langle {/{\rm{italic}}} \rangle $ 12.1. The most frequent indication for renal biopsy was acute kidney injury (26.3%), followed by rapidly progressive renal failure and nephrotic syndrome (22.8%). In our population, 22.9% had DN and 77.4% had NDRD. Pauciimune Glomerulonephritis (14%) and Membranous Nephropathy (10.5%) were the most common causes of NDRD. A chi-square test was performed to examine the relation between the two groups (ND vs NDRD) and the presence of diabetic retinopathy. There was a statistically significant association between the two variables ($\langle {{\rm{italic}}} \rangle {{\rm{X}}}^2\langle {/{\rm{italic}}} \rangle $= 11.778, p&amp;lt;0.01). Mann-Whitney test was performed to compare the median of duration the diabetes and Hb1Ac in two groups. That showed a statistically significant difference (U = 357, P = .018 and U=335.5 P = .013 respectively). Conclusion Since renal biopsy is critical to establish the correct diagnosis and provide an appropriate treatment, it should be performed in patients with high suspicion of NRDN, especially in patients with a recent diagnosis of diabetes, good metabolic control and the absence of diabetic retinopathy.