Biopsy In Diabetic Patients Research Articles

Challenge of Kidney Biopsy in Diabetic Patients: A Northwest Italy Large Cohort

Challenge of Kidney Biopsy in Diabetic Patients: A Northwest Italy Large Cohort

#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 <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.

#6467 DETERMINANTS OF NON-DIABETIC KIDNEY DISEASES IN DIABETIC PATIENTS

Abstract Background and Aims While diabetic nephropathy is the main kidney disease in patients with type 2 diabetes mellitus, a variety of non-diabetic kidney diseases (NDKD) may also occur. The decision to order a biopsy in diabetic patients is not an easy one as diabetic kidney disease is itself a proteinuric condition. The main objective of this study is to define factors that may differentiate isolated diabetic nephropathy and non-diabetic kidney disease in diabetic patients. In addition, we also aimed to analyze the effects of treatment choices on renal and overall survival. Method The study was conducted at a university hospital, which served as a tertiary healthcare center. One hundred and three diabetic patients who underwent kidney biopsy were involved in the study. Demographic characteristics, physical examination findings, laboratory tests and kidney biopsy findings were retrospectively evaluated. Results According to kidney biopsy findings 30 patients (29,1%) had isolated diabetic nephropathy. NDKDs were present in 73 (70,9%) of the patients. 78,1% of the patients with NDKDs had non-diabetic glomerular diseases. Among glomerular diseases, focal segmental glomerulosclerosis (36,9%), IgA nephropathy (17,8%) and membranous nephropathy (13,7%) were the leading three diseases. The duration of diabetes (p=0,00), HBA1C level (p=0,00) and the amount of proteinuria (p=0,02) were higher in patients who had isolated diabetic nephropathy. Presence of diabetic retinopathy (p=0,00), concomitant vascular diseases (p=0,02) and the use of insulin treatment were also more often in patients with isolated diabetic nephropathy. Multivariate analysis revealed that patients with higher HBA1C levels and longer diabetes duration had more tendencies to have isolated diabetic nephropathy. Immunosuppressive treatments for glomerular diseases were administered in around 50% of the patients. However, renal and overall survivals were not different between patients who received immunosuppressive treatments and those who didn't. Conclusion A renal biopsy in diabetic patients might be preserved for those with shorter diabetes duration and lower HBA1C levels. As poor glycemic control and susceptibility to infections pose additional risks, immunosuppressive treatments might not always be beneficial.

#5147 PREDICTING NON-DIABETIC KIDNEY DISEASE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: EXTERNAL VALIDATION OF FOUR PREDICTIVE MODELS

Abstract Background and Aims Several prediction models have been published for estimating the probability of non-diabetic kidney disease in kidney biopsies performed in patients with diabetes mellitus. External validation and comparison of these models is essential prior to their clinical application. The aim of this study was to validate and compare the predictive capacity of four previously described clinical models as a tool to predict non-diabetic kidney disease (NDKD) in diabetic patients. Method We retrospectively reviewed kidney biopsies performed in patients with type 2 diabetes mellitus between January 1999 and December 2022 in our centre. The probability of presence of NDKD was calculated by using the clinical and laboratory parameters at the time of the decision to perform a biopsy, according to 4 models; Surinrat's model, Liu's model, Li's model and Garcia-Martin's model (see Table 1). Overall model fit was assessed, calibration curves were plotted and discrimination for each model was assessed by using the receiver operating characteristic (ROC) curve in line with the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines. Results The study included 280 patients, 68.9% were males and the mean age was 65.4 ± 11.9 years. 172 patients (61.4%) had a diagnosis of non-diabetic kidney disease. On calculating the risk of NDKD, Surinrat's, Li's and Garcia-Martin's models predicted 33.6%, 64.8% and 53.4% of NDKD when using the “probable NDKD” threshold, and 60.7%, 81% and 90.7% respectively when including the “grey zones”. Fleiss’ Kappa test showed a fair agreement between the four models when using the “probable NDKD” threshold (k = 0.23, 95% CI 0.13-0.33, p<0.001) and when including the “grey zones” (k = 0.39, 95% CI 0.29-0.49, p<0.001). On using the “probable NDKD” threshold, the overall accuracy for Surinrat's, Liu's, Li's and Garcia-Martin's models was 50.7%, 62.7%, 63.6% and 65.3% respectively, while on including the “grey zones” the accuracy slightly increased in the first to models to 54.3% and 66.4% respectively while decreasing in Garcia-Martin's model to 64.2%. Area under the ROC curve (AUC) was higher in Garcia-Martin's model (AUC 0.66, 95% CI 0.58-0.74, p<0.001) compared to Lin's model (AUC 0.59, 95% CI 0.50-0.67, p = 0.044), while Surinrat's and Liu's models did not discriminate (AUC 0.55, 95% CI 0.47-0.64, p = 0.214 and AUC 0.58, 95% CI 0.49-0.63, p = 0.084). Conclusion There is a fair agreement between the four models for predicting non-diabetic kidney disease in type 2 diabetic patients. Of the models studied, Garcia-Martin's model most accurately predicted non-diabetic kidney disease in type 2 diabetes patients, although discrimination remained poor. These models may not be suitable for guiding clinicians on indicating a kidney biopsy in diabetic patients in our population.

MO622: Clinical Value of Kidney Biopsy in Patients with Diabetes Mellitus and Nephrotic-Range Proteinuria: Correlation of Clinical and Laboratory Findings with Histopathological Data

Abstract BACKGROUND AND AIMS Diabetes mellitus (DM) is tightly associated with the increased prevalence and rapid evolution of diabetic nephropathy (DN). Interestingly, deterioration of kidney function in diabetic patients is often nonetheless caused by other factors besides DM and frequently goes undiagnosed. Nondiabetic renal disease (non-DRD) could be suspected in case of rapid progression of renal function impairment and/or severe, nephrotic-range proteinuria. While biopsy of the kidneys is the ‘gold standard’ of the diagnostic approach in such cases, no real consensus exists regarding the profile of diabetic patients with renal disease and proteinuria, who should be submitted to kidney biopsy. Thus, this study intends to correlate the clinical and biochemical profile of diabetic patients with deteriorated kidney function to the histopathological data of a kidney biopsy and allows early differentiation between DN and non-DRD based on the results of kidney biopsy. METHOD A total of 32 patients, who were treated in our outpatient's diabetes clinic from a multidisciplinary team of endocrinologists and nephrologists at Evangelismos General Hospital, were retrospectively studied. All patients suffered from DM2 and presented with nephrotic-range levels of proteinuria. Biochemical data of glycemic control and renal function, clinical findings related to DN and histological findings of kidney biopsy were documented. All patients were submitted to kidney biopsy and depending on the histopathologic findings were categorized into three groups: (i) genuine diabetic nephropathy (GDN), (ii) renal disease due to cause other than diabetes mellitus (ODMRD) and (iii) mixed renal disease (MRD). RESULTS Among the 32 patients, 15 (46.9%) had findings of a GDN, while 17 patients (53.1%) suffered from ODMRD (13 patients) or MRD (4 patients). All patients were hypertensive. The patients with GDN were younger (54.1 versus 68.2 versus 70.5 years, P = 0.016) and had a higher HbA1C value (7.9 versus 6.5 versus 6.8%, P = 0.069) at the time of the kidney biopsy in comparison to the ODMRD and MRD patients. On the contrary, ODMRD patients had significantly smaller disease duration compared with the GDN and MRD groups (8.4 versus 11.6 versus 13.3 years, P = 0.04). Furthermore, the incidence of diabetic retinopathy was greater among patients with GDN and MRD in comparison to the ODMRD patients (60 versus 75 versus 7.6%, P < 0.01). Additionally, interstitial fibrosis was significantly more prevalent among the patients with GDN in comparison to those with ODMRD and MRD, respectively (73.3 versus 38.4 versus 50%, P = 0.02). Finally, the presence of diabetic retinopathy {OR 4.88, [95% confidence interval (CI) 1.06–22.38], P = 0.04}, higher levels (>25%) of interstitial renal fibrosis [OR 5.71 (95% CI 1.16–28.1), P = 0.032] and longer DM2 duration (>10 years) [OR 5.04, (95% CI 1.1–22.96), P = 0.036] were recognized as factors, which were positively associated with GDN. CONCLUSIONS This study highlights emphatically the usefulness of the kidney biopsy and its histopathological findings in case of patients with diabetes mellitus and nephrotic-range levels of proteinuria. The value of a detailed and careful medical history seems to be critical for the early diagnosis of the type of kidney disease in diabetic patients. It is crucial to early differentiate the patients who suffer from nondiabetic nephropathy, from those with diabetic nephropathy and initiate the appropriate therapy, according to the underlying cause. Thus, the detection of nephrotic-range levels of proteinuria in diabetic patients should lead to kidney biopsy especially in case diabetic retinopathy is not present and longer disease duration is observed. Finally, the existing criteria/indications for a kidney biopsy in diabetic patients with nephrotic-range levels of proteinuria should be reconsidered or even revised.

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.

Characterizing predictors of non-diabetic kidney disease (NDKD) in diabetic patients.

Diabetic kidney disease (DKD) is the chief cause of renal involvement in diabetic patients. It is primarily a clinical diagnosis. Non-diabetic kidney disease (NDKD) may be missed if they are not biopsied. In this study, we describe the spectrum of NDKD and evaluate the predictors considered for planning a biopsy in diabetic patients with kidney disease. In a retrospective cohort study, diabetic patients who underwent kidney biopsy at our centre between May 2006 and July 2019 were evaluated for NDKD. 321 diabetic patients who underwent kidney biopsy were analyzed. Mean age was 49.3 ± 12.4years and 71% were males. 75.8% patients had hypertension and 25.2% had diabetic retinopathy. Based on the kidney biopsy, patients were classified as DKD-127 (39.6%), NDKD-179(55.8%) and combined DKD + NDKD-15(4.7%). Overall, the most commonly diagnosed pathology was membranous nephropathy-MN (17%), followed by IgA nephropathy (16.0%) and focal segmental glomerulosclerosis-FSGS (14.9%). In patients with DKD + NDKD, IgA nephropathy (53.3%) was predominant. 165 (51.4%) patients had a diagnosis potentially amenable to a specific therapy. On multivariate analysis, female gender [OR 2.07 (1.08-3.97), p = 0.02], absence of diabetic retinopathy [OR 7.47 (3.71-15), p < 0.001] absence of hypertension [OR 3.17 (1.56-6.45), p = 0.001] and duration of diabetes ≤ 24months [OR 3.67(1.97-6.84), p < 0.001], were independent predictors for NDKD while the absence of nephrotic range proteinuria [OR 1.73 (0.98-3.05), p 0.05] showed a trend towards significance. Astute use of kidney biopsy can detect potentially treatable NDKD in a large number of diabetic patients with glomerular diseases being the predominant diagnosis. A combination of risk factors needs to be considered to guide the need for kidney biopsy in diabetic patients.

Clinical Predictors of Nondiabetic Kidney Disease in Patients with Diabetes: A Single-Center Study

Background Although diabetic kidney disease (DKD) could affect up to one-third of patients with diabetes mellitus (DM), these patients can develop kidney diseases different from DKD, or these conditions can superimpose on DKD. Several potential predictors of nondiabetic kidney disease (NDKD) have been proposed, but there are no definitive indications available for kidney biopsy in diabetic patients. Methods We designed a single-center, cross-sectional, and retrospective cohort study to identify clinical and laboratory factors associated with a diagnosis of NDKD after native kidney biopsy in diabetic patients and to investigate differences in time to end-stage kidney disease (ESKD) in patients with a diagnosis of DKD and NDKD. Results Of 142 patients included in our analysis, 89 (62.68%) had a histopathological diagnosis of NDKD or mixed NDKD + DKD. Patients in the NDKD group had significantly lower HbA1C, lower prevalence of diabetic retinopathy (DR), and less severe proteinuria, and there was a lower proportion of patients with nephrotic syndrome; the DKD group had significantly lower proportion of patients with hematological conditions. In the multivariate binary logistic regression, only absence of DR and presence of a hematological condition significantly predicted NDKD after adjustment for age and sex. Time to ESKD was significantly higher in patients with NDKD or mixed forms than in those with DKD. Conclusions After a careful selection, more than half of kidney biopsies performed in diabetic patients can identify NDKD (alone or with concomitant DKD). Absence of DR and coexistence of a hematological condition (especially MGUS) were strong predictors of NDKD in our cohort.

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 Disease in Patients with Type 2 Diabetes Mellitus with Proteinuria

Background: Diabetes mellitus (DM) is the leading cause of end stage renal disease (ESRD) worldwide. Although DM with proteinuria is the ultimate result of diabetic nephropathy (DN), a wide spectrum of non-diabetic renal diseases (NDRD) can occur in such patients. Objective: To observe the frequency and histological pattern of NDRD in diabetic patients with proteinuria and to explore their association with clinical and laboratory parameters. Methods: This cross-sectional study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from April 2016 to September 2017. In this study a total of 38 cases of DM with proteinuria (>1 gm/24-hour) were selected purposively. Renal biopsy was done in all patients. Based on histological findings they were categorized into two groups; Group 1 with NDRD and Group II with DN. Their clinical and laboratory parameters were analyzed and compared. Results: Among the total study subjects, 21 (55.3%) were male and 17 (44.7%) were female, mean (±SD) age 43.45 ± 9.99 years in the NDRD group and 41.57 ± 9.50 years in the DN group. Thirty one cases (81.6%) out of thirty eight had NDRD and seven (18.4%) cases had isolated DN; therefore more than two third cases had NDRD. Duration of DM was found to be significantly shorter (p = 0.004) in the NDRD group. Diabetic retinopathy was present in 12.9% cases in NDRD group vs. 57.1% cases in DN group (p = 0.025). Frequency of microscopic hematuria was significantly higher (90.3%) in NDRD patients (p = 0.002). Conclusion: The frequency of NDRD in type 2 diabetic patients other than diabetic nephropathy is relatively high. Membrano proliferative glomeru-lonephritis and membranous nephropathy are more common in NDRD. Absence of diabetic retinopathy, presence of hematuria and shorter duration of DM are markers associated with NDRD in type 2 DM, which are important indicators for renal biopsy in diabetic patients with proteinuria.

The current role of renal biopsy in diabetic patients.

Diabetes mellitus (DM) is a worldwide health problem due to its high prevalence, incidence and impact on patient morbidity and mortality. Chronic kidney disease (CKD) is one of the most important complications of DM. The indication of renal biopsy in diabetic patients is a widely debated topic and the final decision is usually individualized. The results of renal biopsy in diabetic patients can be classified into three groups: diabetic nephropathy (DN), non-diabetic renal disease (NDRD) or DN plus NDRD (mixed forms). Renal involvement in DN has been widely studied and different pathological classifications have been proposed. Some groups demonstrated a relationship between the pathological classifications in DN and renal prognosis. However, to our knowledge renal biopsy in diabetic patients with DN has not demonstrated an impact on their survival and renal prognosis. Some recent studies suggest that non-proteinuric diabetic patients may be affected of DN. In addition, kidney biopsy in DN under new treatments may have a fundamental role in assessing renal protection or even regression of diabetic histological lesions. On the other hand, the accurate and early diagnosis and subsequent treatment of diabetic patients with NDRD has been shown to benefit both their renal and patient prognosis. Renal involvement in patients with DM is very heterogeneous. Thus, the role of renal biopsy in diabetic patients is becoming increasingly important.

Renal biopsy in diabetic patients (experience of Nephrology Department of Clinic for Internal Diseases UCC Banjaluka)

&amp;lt;p&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.119px; top: 394.957px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.16849);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;Introduction&amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 214.402px; top: 394.957px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.11335);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;. Apart from diabetic nephropathy diabetic patients may experience a nondiabetic kidney &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 414.964px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.06783);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;disease and the kidney biopsy is the best way to diagnose it. The aim of the study is to show the frequency &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 434.964px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.11251);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;und type of nondiabetic kidney disease diagnosed by kidney biopsy in diabetic patients.&amp;lt;/span&amp;gt;&amp;lt;br role=&amp;quot;presentation&amp;quot; /&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 464.414px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.15857);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;Methods&amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 185.694px; top: 464.414px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.1105);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;. We presented the results of renal biopsy in diabetic patients performed at the Department of &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 484.414px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.09154);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;Nephrology Clinic for Internal Medicine from April 2007 to May 2013. During the period nine biopsies &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 504.414px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.12858);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;in diabetic patients were performed (from the total of 157). The biopsy was performed with a biopsy &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 524.413px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.1368);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;gun- Gun Fast with 16G needle diameter, under control of ultrasound device (Toshiba Famio 5 with&amp;lt;/span&amp;gt;&amp;lt;br role=&amp;quot;presentation&amp;quot; /&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 544.413px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.10315);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;probe guide). Two tissue samples were taken: one for optical microscopy and the other for immunoflu&amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 564.413px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.09241);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;orescence. The mean duration of diabetes was 4.9 years, in two men and seven women. One patient had &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 584.413px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.12583);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;retinopathy, whereas seven patients had hypertension.&amp;lt;/span&amp;gt;&amp;lt;br role=&amp;quot;presentation&amp;quot; /&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 613.863px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.15009);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;Results&amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 174.56px; top: 613.863px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.0997);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;. The indications for biopsy in our diabetic patients were: six patients with nephrotic syndrome, &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 633.862px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.08362);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;two with asymptomatic urinary abnormalities (persistent proteinuria and/or microhematuria), one patient &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 653.862px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.1217);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;with systemic lupus erythematosus. Six patients had a histological diagnosis of diabetic nephropathy, &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 673.862px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.12002);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;two patients had diabetic nephropathy combined with other disease (one combined with hypertensive&amp;lt;/span&amp;gt;&amp;lt;br role=&amp;quot;presentation&amp;quot; /&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 693.862px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.14594);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;nephroangiosclerosis and the other with lupus nephritis), and one patient had primary membranous &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 713.862px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.12085);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;glomerulonephritis.&amp;lt;/span&amp;gt;&amp;lt;br role=&amp;quot;presentation&amp;quot; /&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 743.311px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.15026);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;Conclusion&amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 205.47px; top: 743.311px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.14154);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;. Renal biopsy in our nine patients with diabetes showed that three patients (33.3%) had &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 763.311px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.15765);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;nondiabetic kidney disease. In total, two out of three patients with nondiabetic kidney disease had &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 783.311px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.11173);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;glomerulal disease and one had vascular disease (hypertensive nephroangiosclerosis). Although fewer &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 803.311px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.10269);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;patients were considered in comparison to the studies of the other authors, our first experience shows a &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 823.311px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.08519);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;significant percentage of diabetic patients with nondiabetic kidney disease, which can only be diagnosed &amp;lt;/span&amp;gt;&amp;lt;span dir=&amp;quot;ltr&amp;quot; style=&amp;quot;left: 118.11px; top: 843.311px; font-size: 16.6667px; font-family: serif; transform: scaleX(1.1154);&amp;quot; role=&amp;quot;presentation&amp;quot;&amp;gt;and confirmed by kidney biopsy.&amp;lt;/span&amp;gt;&amp;lt;/p&amp;gt;

Minimal change disease associated with type 1 and type 2 diabetes mellitus

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents.

Clinical Predictors of Non-diabetic Renal Disease and Role of Renal Biopsy in Diabetic Patients with Renal Involvement: A Single Centre Review

Background: Type 2 diabetes mellitus (T2DM) is reportedly the leading cause of end-stage renal disease (ESRD) worldwide. However, non-diabetic renal diseases (NDRD) are not uncommon among T2DM patients with renal involvement. Our study aimed to examine the prevalence of NDRD in T2DM and clinical markers for diabetic nephropathy (DN) and NDRD and to determine the role of renal biopsy in T2DM patients and its impact on clinical practice. Methods: We conducted a retrospective analysis of T2DM patients in whom renal biopsies were performed from January 2004 to March 2008 (n = 110). Results: Biopsy results were divided into three groups: group I/pure DN (62.7%), group II/isolated NDRD (18.2%), and group III/mixed lesions (19.1%). The causes of NDRD in decreasing order of frequency were acute interstitial nephritis, glomerulonephritides, hypertensive renal disease, and acute tubular necrosis. Significant clinical markers for DN are presence of diabetic retinopathy and longer duration of diabetes. For NDRD, useful clinical markers include the presence of acute renal failure and microscopic hematuria. In the DN subgroup, Indians had significantly shorter duration of diabetes on biopsy compared with Malays and Chinese. Conclusions: NDRD is prevalent in T2DM patients, and given its potentially treatable nature, renal biopsy should be considered in T2DM patients with nephropathy, especially in those with atypical features.

Proteome analysis of laser microdissected glomeruli from formalin-fixed paraffin-embedded kidneys of autopsies of diabetic patients: nephronectin is associated with the development of diabetic glomerulosclerosis

To date, little proteomic information has been available from the glomeruli of diabetic patients, possibly due to the clinical limitations of renal biopsy in diabetic patients and insufficient quantities of such specimens for proteome analysis. The purpose of the present study was to identify altered protein expression profiles in diabetic glomeruli using formalin-fixed paraffin-embedded (FFPE) kidney tissues from diabetic patients. Glomeruli were laser microdissected from FFPE autopsy kidney tissues from 10 patients with diabetic nephropathy and 10 non-diabetic control patients and underwent proteome analysis using QSTAR Elite liquid chromatography with tandem mass spectrometry and iTRAQ technology. Immunohistochemical analysis was performed on 93 autopsy samples from diabetic patients with and without nephropathy (n = 45 and n = 48, respectively). Thirty-one renal and urological disease-related proteins displayed a differential abundance in glomerular samples from patients with diabetic nephropathy compared with non-diabetic control patients. Among them, we found that nephronectin, which functions in the assembly of extracellular matrix, showed clearly positive immunoreactivity in diabetic glomeruli. The numerical fraction of nephronectin-positive glomerular cross sections was increased significantly in diabetic patients with nephropathy compared to those without nephropathy (32.1 ± 31.5 versus 4.14 ± 5.65%, P < 0.0001). Furthermore, there was a significant positive correlation between this numerical fraction of nephronectin-positive glomerular cross sections and the glomerular sclerosis index (ρ = 0.881, P < 0.0001, n = 93). The present study demonstrated, for the first time, that nephronectin may be associated with the development of diabetic glomerulosclerosis and that proteome analysis with FFPE kidney tissues from diabetic patients with nephropathy is useful in understanding diabetic nephropathy.

Prevalence of Nondiabetic Renal Disease in Diabetic Patients

Background: Diabetic nephropathy is the leading cause of end-stage renal disease in the USA, yet most patients with type 2 diabetes mellitus are not formally evaluated with a renal biopsy. Our aim was to evaluate the prevalence of nondiabetic renal disease (NDRD) in patients with type 2 diabetes mellitus to determine common clinical indicators suggestive of NDRD. Methods: A retrospective analysis was performed on biopsy reports of patients who had undergone native renal biopsy between January 1, 1995, and December 31, 2005. Results: After exclusion of 57 patients, 233 patients with DM2 were included in our analysis. Mean age at the time of biopsy was 58.1 ± 13.7 years, and 53.0% of the study population were male. There were 124 cases (53.2%) with a pathologic diagnosis of NDRD, 64 (27.5%) with pure diabetic glomerulosclerosis (DGS) and 45 (19.3%) with concurrent NDRD and DGS (CD). Patients with NDRD tended to be younger than those with DGS and had significantly less associated diabetic retinopathy. Focal segmental glomerulosclerosis was the most common lesion found in patients with NDRD and accounted for 21.0% of all NDRD, followed by minimal-change disease (15.3%). IgA nephropathy (15.6%) and membranous glomerulonephritis (13.3%) were the most prevalent lesions found in patients with CD. Conclusions: The high prevalence of NDRD found in our population underscores the need for clinicians to consider renal biopsy in diabetic patients with an atypical clinical course, since additional disease-specific therapies may be helpful for this subset of the population.

Clinical features of non-diabetic renal diseases in patients with type 2 diabetes

Although persistent proteinuria is characteristic of diabetic nephropathy (DN), it is important to differentiate non-diabetic renal diseases (NDRD) in diabetic patients with proteinuria. In order to re-evaluate the indications for renal biopsy in the diabetic patients, we retrospectively analyzed the relationship between clinical features and histological diagnosis in 97 Japanese patients with type 2 diabetes manifesting overt proteinuria. Renal biopsy was performed because they were clinically suspected to have NDRD. Patients were divided into three groups according to the histological diagnosis: (1) the DN group ( n = 35) had only diabetic lesions, (2) the complicated group ( n = 16) had histological changes of NDRD superimposed on DN and (3) the non-DN group ( n = 46) had NDRD without diabetic lesions. We evaluated the specificity and sensitivity of four clinical parameters (duration of diabetes, presence or absence of diabetic retinopathy, microscopic hematuria and granular casts as urinary sediments) for the prediction of NDRD. Short duration of diabetes (<5 years) showed high sensitivity (75%) and specificity (70%). Diabetic retinopathy showed the highest sensitivity (87%) and specificity (93%). The sensitivity and specificity of microscopic hematuria (56 and 58%) and granular casts (68 and 47%) were lower. Our study confirmed that the absence of retinopathy and short duration of diabetes are useful clinical indications for renal biopsy in diabetic patients with overt proteinuria.

AUTOIMMUNE DIABETIC NEUROPATHY

Recent work has shown that inflammatory vasculopathy is commonly seen in biopsies of diabetic patients with neuropathy. Most of these patients have had syndromes consistent with proximal diabetic neuropathy or amyotrophy. This suggests that inflammatory vasculopathy is important in the pathogenesis of these disorders. Immunosuppressive therapy may benefit many of these patients.

Ureteral obstruction of renal transplant due to ureteral candidiasis

In a diabetic renal transplant recipient a nephrocutaneous fistula developed after percutaneous renal graft biopsy, and ureteral obstruction due to Candida albicans fungus balls was demonstrated. Local irrigation with amphotericin B, systemic antifungal therapy, and rigid blood sugar control led to rapid clearing of the fungal infections. This cause of renal transplant insufficiency should be considered prior to renal biopsy in diabetic patients with yeast forms in the urine.