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.

BACKGROUND: 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. PURPOSE: To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM. STUDY TYPE: Prospective. POPULATION: Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD). FIELD STRENGTH/SEQUENCE: 3 T/ T2 weighted imaging (T2WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: 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. STATISTICAL TESTS: 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. RESULTS: 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). DATA CONCLUSION: 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. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS: Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

[Value of Contrast-enhanced Ultrasound Parameters in Evaluating K-W Nodule Formation in Diabetic Nephropathy].

Objective To discuss the value of contrast-enhanced ultrasound(CEUS)parameters in evaluating the formation of Kimmelstiel-Wilson(K-W)nodules in diabetic nephropathy(DN).Methods Sixty-two patients pathologically diagnosed with DN and undergoing CEUS in the First Medical Center of Chinese PLA General Hospital from March 2017 to January 2020 were assigned into two groups according to whether K-W nodules were formed.The cortical CEUS parameters and the ratios of cortical to medullary CEUS parameters were compared between the two groups.Results The 62 patients included 19 patients without K-W nodules(group A)and 43 patients with K-W nodules(group B).The median rise time(U=209,P=0.013)and fall time(U=197,P=0.007)in group B were significantly longer than those in group A.The median wash-in rate(WiR)(U=228,P=0.031)and wash-out rate(WoR)(U=229,P=0.032)in group B were significantly lower than those in group A.The median peak enhancement(PE)1/PE2(U=224,P=0.026),WiR1/WiR2(U=235,P=0.041),and WoR1/WoR2(U=230,P=0.043)ratios in group B were significantly lower than those in group A.The median FT1/FT2 ratio in group B was significantly higher than that in group A(U=227,P=0.038).Conclusion CEUS parameters can be used to quantitatively evaluate renal cortical microperfusion in DN patients with K-W nodules.

GLA missense and promoter variants co-segregating in a Chinese family with Fabry disease.

BACKGROUND: Fabry disease (FD) is an X-linked recessive inheritance lysosomal storage disorder due to mutations in the GLA gene leading to deficiency of lysosomal α-galactosidase A (α-Gal A) and has a wide range of clinical presentations. Over 900 GLA gene mutations are currently known and of those most are thought not to be clinically significant, some with doubtful clinical significance, posing diagnostic and prognostic difficulties for the clinician. METHODS: Whole-exome sequencing (WES) was performed to detect the mutation in family members with Fabry disease. The function of g.1170C>T mutation was confirmed by dual luciferase system. RESULTS: A total of 1,375 variants were found in a Chinese family with FD. A missense variants c.1025C>T (p.Arg342Gln) which have been previously reported in association with FD and g.1170C>T single-nucleotide polymorphism (SNP) in the GLA gene were found in five patients. The g.1170C>T SNP affects transcription of GLA gene, presumably the transcription start site. Female patients only have hypohidrosis and neuropathic pain, while male patients have severe symptoms with simultaneous renal impairment. CONCLUSIONS: Two simultaneous variants in cis of the GLA gene, c.1025C>T (p.Arg342Gln) and g.1170C>T, were verified in Chinese individuals, and the corresponding clinical symptoms were described. The disease severity in male patients is worse than in female patients. These results may be helpful for genetic counseling, diagnosis and prognosis of patients with FD.

Diagnostic efficacy of serum anti-phospholipase A2 receptor antibodies for idiopathic membranous nephropathy in patients with diabetic kidney disease.

AIM: Serum anti-phospholipase A2 receptor (anti-PLA2R) antibodies are highly accurate in diagnosing idiopathic membranous nephropathy (IMN) in populations with kidney disease. However, the diagnostic value of anti-PLA2R antibodies for IMN in diabetic kidney disease (DKD) is unclear. The objective of this study is to determine the diagnostic efficacy and the optimal cut-off value of this marker in populations with DKD. METHODS: This study included 227 patients with type 2 diabetes who were admitted to the Department of Nephrology of the Chinese People's Liberation Army General Hospital from May 2016 to January 2018 and underwent pathological diagnosis by renal biopsy. Anti-PLA2R antibodies were detected by enzyme-linked immunosorbent assay in this population. According to the pathological results, the participants were divided into an IMN group and non-membranous nephropathy (non-MN) group. The clinical characteristics were analyzed, the diagnostic ability of anti-PLA2R antibodies was evaluated, and the receiver operating characteristic (ROC) curve was constructed to obtain the optimal cut-off value. RESULTS: There were 45 patients in the IMN group, accounting for 19.8% of the study sample. The patients in this group were older at the time of renal biopsy than the non-MN group and presented a shorter duration of diabetes, better glycemic control, lower blood pressure and uric acid, and better renal function; in addition, their clinical symptoms indicated nephrotic syndrome. The optimal cut-off value for anti-PLA2R antibodies for the diagnosis of IMN in DKD was 2.71 Ru/ml, sensitivity was 0.800, specificity was 0.951, positive predictive value was 0.800, negative predictive value was 0.951, accuracy was 0.921, and the Yoden index was 0.750. The area under the ROC curve was 0.87 (95% CI, 0.788-0.952) (p < 0.001). CONCLUSIONS: Patients in the IMN group were older, had better renal function and general condition, and the clinical symptoms indicated nephrotic syndrome. Anti-PLA2R antibodies had a good diagnostic performance for IMN in the population with DKD, and the optimal cut-off value was 2.71.

Validation of the 2007 kidney disease outcomes quality initiative clinical practice guideline for the diagnosis of diabetic nephropathy and nondiabetic renal disease in Chinese patients.

AIMS: Diabetes mellitus (DM) has overtaken infection and immunological factors as the most common cause of end-stage renal disease. The 2007 Kidney Disease Outcomes Quality Initiative (KDOQI) guideline is a widely accepted guideline for the clinical diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD). Our study sought to verify its diagnostic ability in the Chinese population. METHODS: We included 773 patients with DM who underwent a renal biopsy at the Chinese PLA General Hospital from 2007 to 2016. All patients were divided into three groups according to their pathological findings: isolated DN, isolated NDRD, and DN combined with NDRD. RESULTS: Good sensitivity and poor specificity were found for the prediction of NDRD in the Chinese population. Rapidly decreasing estimated glomerular filtration rate, systemic disease, refractory hypertension, and the existence of "grey area" patients may have contributed to the poor diagnostic ability. CONCLUSIONS: The diagnostic ability of the 2007 KDOQI guideline for DN and NDRD was unsatisfactory. The high sensitivity and low specificity of the guideline made it more suitable as screening criteria rather than as diagnostic criteria.

Identification of key genes and pathways in diabetic nephropathy by bioinformatics analysis.

AIMS/INTRODUCTION: The aim of the present study was to identify candidate differentially expressed genes (DEGs) and pathways using bioinformatics analysis, and to improve our understanding of the cause and potential molecular events of diabetic nephropathy. MATERIALS AND METHODS: Two cohort profile datasets (GSE30528 and GSE33744) were integrated and used for deep analysis. We sorted DEGs and analyzed differential pathway enrichment. DEG-associated ingenuity pathway analysis was carried out. The screened gene expression feature was verified in the db/db mouse kidney cortex. Then, rat mesangial cells cultured with high-concentration glucose were used for verification. The target genes of transcriptional factor E26 transformation-specific-1 (ETS1) were predicted with online tools and validated using chromatin immunoprecipitation assay quantitative polymerase chain reaction. RESULTS: The two GSE datasets identified 89 shared DEGs; 51 were upregulated; and 38 were downregulated. Most of the DEGs were significantly enriched in cell adhesion, the plasma membrane, the extracellular matrix and the extracellular region. Quantitative reverse transcription polymerase chain reaction analysis validated the upregulated expression of Itgb2, Cd44, Sell, Fn1, Tgfbi and Il7r, and the downregulated expression of Igfbp2 and Cd55 in the db/db mouse kidney cortex. Chromatin immunoprecipitation assay quantitative polymerase chain reaction showed that Itgb2 was the target gene of transcription factor Ets1. ETS1 knockdown in rat mesangial cells decreased integrin subunit beta 2 expression. CONCLUSION: We found that EST1 functioned as an important transcription factor in diabetic nephropathy development through the promotion of integrin subunit beta 2 expression. EST1 might be a drug target for diabetic nephropathy treatment.

Clinicopathological Features of Nondiabetic Renal Diseases from Different Age Groups: An Observational Cross-sectional Study.

BACKGROUND: Diabetes mellitus (DM) has become the leading cause of chronic kidney disease (CKD). Nondiabetic renal diseases (NDRDs) have different clinicopathological features and prognosis from those of diabetic nephropathy. Our study sought to analyze the clinical and pathological features of NDRDs, in different age groups through a cross-sectional study. METHODS: All patients with type 2 DM at our center who underwent renal biopsy between March 1997 and March 2017 were screened and divided into three groups by age: Group 1 (youth group), 18-44 years old; Group 2 (middle-aged group), 45-59 years old; and Group 3 (elderly group), ≥60 years old. We analyzed the clinicopathological data and risk factors by univariate and multivariate logistic regression for NDRD of the patients to identify the features of NDRD in different age groups. RESULTS: We included 982 patients in the final analysis. Patients with NDRD accounted for 64.4% of all patients. IgA nephropathy (IgAN) was the most common pathological pattern in young patients with NDRD, accounting for 26.3%. In the middle-aged group, the two most common pathological patterns were IgAN and membranous nephropathy. Membranous nephropathy was the most common pathological pattern in elderly patients with NDRD, accounting for 29.3%. Consistent with pathological features, glomerular hematuria is a risk factor for NDRD in Group 1 (odds ratio [OR], 26.514; 95% confidence interval [CI], 2.503-280.910; P = 0.006). On the other hand, rapidly increasing proteinuria or nephrotic syndrome is a risk factor for NDRD in Group 2 (OR, 5.921; 95% CI, 2.061-17.013; P = 0.001) and Group 3 (OR, 90.409; 95% CI, 6.198-1318.826; P = 0.001). CONCLUSIONS: This single-center study showed that the proportion and composition of NDRD differ among different age groups. Consistent with pathological features, some clinical indices such as hematuria and proteinuria showed different features among different age groups.

Renal Light Chain Deposition Associated with the Formation of Intracellular Crystalline Inclusion Bodies in Podocytes: A Rare Case Report.

We herein report the case of an elderly woman with bone pain and proteinuria as the main clinical manifestations. The patient was diagnosed with the IgG κ type of multiple myeloma. Her renal pathology consisted of widespread κ light chain protein deposition associated with the formation of large quantities of rod-like crystals in podocytes. This phenomenon is very rare. We explored the significance of this crystal formation via a detailed and descriptive analysis and also performed a literature review, thus providing data to increase the available information about this type of disease.

Dysmorphic erythrocytes are superior to hematuria for indicating non-diabetic renal disease in type 2 diabetics.

AIMS/INTRODUCTION: There are sparse and limited studies on erythrocyte morphology in renal biopsy identifying nephropathic patients among type 2 diabetics. The present study sought to clarify the predictive value of dysmorphic erythrocytes in type 2 diabetics with non-diabetic renal disease and influences on hematuria. MATERIALS AND METHODS: We examined 198 patients with type 2 diabetes who underwent kidney biopsies between 2012 and 2013. Hematuria was defined as >3 or >10 red blood cells per high-power field (RBCs/hpf) in urine sediment. If >80% of the erythrocytes were dysmorphic, glomerular hematuria was diagnosed. Clinical findings and predictive value of dysmorphic erythrocytes were compared between patients with hematuria (n = 19) and those without (n = 61). The potential risk factors for hematuria among diabetic nephropathy patients were also screened. RESULTS: There was a statistically significant difference between the diabetic nephropathy group and the non-diabetic renal disease group (6.6 vs 16.8%; P = 0.04) when the demarcation point of hematuria was 10 RBCs/hpf. When the definition of hematuria was based on an examination of urinary erythrocyte morphology, a marked difference was seen (3.3 vs 24.8%; P < 0.001). Glomerular hematuria showed high specificity and a positive predictive value (0.97 and 0.94, respectively) in non-diabetic renal disease. A multivariate analysis showed that nephrotic syndrome was significantly associated with hematuria (odds ratio 3.636; P = 0.034). CONCLUSIONS: Dysmorphic erythrocytes were superior to hematuria for indicating non-diabetic renal disease in type 2 diabetics. Nephrotic syndrome was an independent risk factor for hematuria.

Multiple myeloma with a previous diagnosis of focal segmental glomerulosclerosis: A case report and review of the literature.

The presentation of focal segmental glomerulosclerosis (FSGS) and multiple myeloma (MM), either together or in succession, is extremely rare. Only nine studies have previously reported this poorly understood association. The present study reports the case of a 45-year-old male with FSGS that was diagnosed by a renal biopsy performed for nephrotic syndrome (NS). The patient was admitted to the Chinese People's Liberation Army General Hospital one year later with a fever, anemia, unresolved NS and renal insufficiency. The patient was diagnosed with MM and a renal biopsy was repeated, the results of which suggested renal amyloidosis. The MM was treated with three cycles of vincristine, doxorubicin and dexamethasone chemotherapy. A review of the literature indicated that monoclonal gammopathy may lead to FSGS. It suggested that FSGS patients who are >40 years old should be routinely screened for plasma cell proliferative disorders to guide the treatment, determine a prognosis, achieve primary disease remission and avoid end-stage renal disease.