Medullary sponge kidney with IgA nephropathy: a case report and literature review.

BACKGROUND: Medullary sponge kidney (MSK)is rare in association with glomerulonephritis. We report a patient with medullary sponge kidney, and the kidney biopsy revealed a diagnosis of IgA nephropathy. CASE PRESENTATION: A 27-year-old female presented with hematuria and proteinuria, and imaging studies indicated the presence of medullary spongy kidney. With appropriate preparation, a kidney biopsy was performed. Considering the patient's clinical and pathological characteristics, the final diagnosis was determined to be medullary sponge kidney associated by IgA nephropathy. The combination of corticosteroids and angiotensin receptor blockers (ARBs) proved to be significantly effective in reducing proteinuria in the current case. To the best of our knowledge, this is the first reported case that demonstrates the coexistence of MSK and IgA nephropathy. CONCLUSIONS: Administering precise therapy based on renal pathology can potentially enhance outcomes for patients with renal conditions, necessitating the need for clinicians to be vigilant about differential diagnosis in order to reduce the rates of missed diagnoses and misdiagnosis.

Association of Lung Ultrasound B-Lines with Left Ventricular Diastolic Function in Clinically Euvolemic Haemodialysis Patients.

INTRODUCTION: Left ventricular diastolic dysfunction (LVDD) frequently occurs in haemodialysis patients and is associated with adverse outcomes. Lung ultrasound (LUS) has been recently proposed for the quantification of extravascular lung water through assessment of B-lines. LUS findings and their relationship with LVDD in clinically euvolemic haemodialysis patients were investigated in this study. METHODS: Echocardiography and LUS examinations were performed on each patient. Multivariate linear regression and forward stepwise logistic regression were performed to determine the relationship between B-lines and LVDD. A receiver operating characteristic (ROC) curve with area under the curve (AUC) was calculated to determine the accuracy of B-lines for evaluating LVDD. RESULTS: A total of 119 patients were enrolled. The number of B-lines was statistically related to echocardiographic parameters (LAVI, LVEDVI, E/A, and E/e') of diastolic function, while the relationship between B-lines and LVEF disappeared after adjusting for potential confounding factors. Additionally, compared with the mild B-line group (B-lines: <14), the moderate (B-lines: 14-30) and severe B-line groups (B-lines: >30) were associated with an increased risk of LVDD (OR 24.344, 95% CI 4.854-122.084, p < 0.001, and OR 94.552, 95% CI 9.617-929.022, p < 0.001, respectively). Furthermore, the AUC of the ROC curve for B-lines predicting LVDD was 0.845, and the cut-off of B-lines was 14.5 (sensitivity 64.91%, specificity 93.55%). CONCLUSION: LUS B-lines were closely associated with left ventricular diastolic function in clinically euvolemic haemodialysis patients. Moreover, our findings suggested a B-line ≥14.5 as a reliable cut-off value for identifying patients with LVDD. LUS B-lines may be used as a novel indicator for evaluating LVDD.

Long non­coding RNA L13Rik promotes high glucose-induced mesangial cell hypertrophy and matrix protein expression by regulating miR-2861/CDKN1B axis.

Background: Diabetic nephropathy (DN) is a frequent microvascular complication of diabetes. Glomerular mesangial cell (MC) hypertrophy occurs at the initial phase of DN and plays a critical role in the pathogenesis of DN. Given the role of long non coding RNA (lncRNA) in regulating MC hypertrophy and extracellular matrix (ECM) accumulation, our aim was to identify functional lncRNAs during MC hypertrophy. Methods: Here, an lncRNA, C920021L13Rik (L13Rik for short), was identified to be up-regulated in DN progression. The expression of L13Rik in DN patients and diabetic mice was assessed using quantitative real-time PCR (qRT-PCR), and the function of L13Rik in regulating HG-induced MC hypertrophy and ECM accumulation was assessed through flow cytometry and western blotting analysis. Results: The L13Rik levels were significantly increased while the miR-2861 levels were decreased in the peripheral blood of DN patients, the renal tissues of diabetic mice, and HG-treated MCs. Functionally, both L13Rik depletion and miR-2861 overexpression effectively reduced HG-induced cell hypertrophy and ECM accumulation. Mechanistically, L13Rik functioned as a competing endogenous RNA (ceRNA) to sponge miR-2861, resulting in the de-repression of cyclin-dependent kinase inhibitor 1B (CDKN1B), a gene known to regulate cell cycle and MC hypertrophy. Conclusions: Collectively, the current results demonstrate that up-regulated L13Rik is correlated with DN and may be a hopeful therapeutic target for DN.

[Effects of moxibustion at Yongquan (KI 1) on cognition function and lower limb motor function in patients with post-stroke cognitive impairment of kidney essence deficiency].

OBJECTIVE: To observe the effects of moxibustion at Yongquan（KI 1） on the cognitive function and lower limb motor function in patients with post-stroke cognitive impairment of kidney essence deficiency. METHODS: Eighty-four patients with post-stroke cognitive impairment of kidney essence deficiency were randomly divided into an observation group（42 cases，1 case dropped off）and a control group（42 cases，1 case dropped off）.The control group was treated with medication，electroacupuncture，rehabilitation training and repetitive transcranial magnetic stimulation（rTMS）；on the basis of the treatment as the control group，moxibustion at bilateral Yongquan（KI 1）was adopted in the observation group.Both groups were treated once a day，5 days a week with 2-day interval，4 weeks were required. The Montreal cognitive assessment (MoCA) score, mini-mental state examination (MMSE) score, Fugl-Meyer assessment-lower extremity (FMA-LE) score, Berg balance scale (BBS) score, functional independence measure (FIM) score, modified fall efficacy scale (MFES) score and scale for the differentiation of syndromes of vascular dementia (SDSVD) score before and after treatment were observed in the two groups. RESULTS: After treatment，the MoCA, MMSE, FMA-LE, BBS, FIM and MFES scores were higher than those before treatment in both groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05). After treatment，the SDSVD scores were lower than those before treatment in both groups (P< 0.05), and the SDSVD score in the observation group was lower than that in the control group (P< 0.05). CONCLUSION: Moxibustion at Yongquan（KI 1） can improve the cognitive function and motor and balance function of lower limbs in patients with post-stroke cognitive impairment of kidney essence deficiency，reduce the risk of fall and improve the quality of life.

Breviscapine alleviates podocyte injury by inhibiting NF-κB/NLRP3-mediated pyroptosis in diabetic nephropathy.

Podocyte injury is a critical factor in the pathogenesis of diabeticnephropathy (DN). Emerging evidence has demonstrated that breviscapine (Bre) exerts a renoprotective effect on diabetic rats. However, the effects of Bre on regulating podocyte injury under high glucose (HG) conditions remain unclear. In this study, an experimental mouse model of DN was induced by intraperitoneal injections of streptozotocin (STZ) in vivo. The effects of Bre on podocyte injury were assessed using cell counting kit-8 (CCK-8) assay, TdT-mediated dUTPnick-endlabelling (TUNEL) staining, quantitative real-time PCR (qRT‒PCR) and western blot analysis. We found that renal function was significantly decreased in diabetic mice, and this effect was blocked by Bre treatment. Bre effectively increased podocyte viability and inhibited HG-induced cell apoptosis. Furthermore, Bre ameliorated HG-induced podocyte injury, as evidenced by decreased α-smooth muscle actin (α-SMA) expression and increased podocin and synaptopodin expression. Mechanistically, Bre inhibited HG-induced nuclear factorkappaB (NF-κB) signalling activation and subsequently decreased NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, resulting in a decrease in pyroptosis. Pharmacological inhibition of NLRP3 decreased HG-induced podocyte injury, whereas the NLRP3 agonist abrogated the effects of Bre on inhibiting podocyte injury. In summary, these results demonstrate that Bre alleviates HG-induced podocyte injury and improves renal function in diabetic mice, at least in part by inhibiting NF-κB/NLRP3-mediated pyroptosis.

[Governor vessel moxibustion combined with warming acupuncture for knee osteoarthritis with yang deficiency and cold congelation based on the supporting-yang theory].

OBJECTIVE: To compare the clinical efficacy between governor vessel moxibustion combined with warming acupuncture based on the supporting-yang theory and simple warming acupuncture for knee osteoarthritis (KOA) with yang deficiency and cold congelation. METHODS: A total of 64 patients with KOA of yang deficiency and cold congelation were randomized into a combination group (32 cases, 2 cases dropped off) and a warming acupuncture group (32 cases, 1 case dropped off). In the warming acupuncture group, warming acupuncture was applied at Zusanli (ST 36), Guanyuan (CV 4) and Dubi (ST 35), Neixiyan (EX-LE 4), etc. on the affected side, once a day. On the basis of the treatment in the warming acupuncture group, governor vessel moxibustion was applied in the combination group, once a week. The 14-day treatment was taken as one course, and totally 2 courses with 2-day interval were required in the two groups. The clinical symptom score, the visual analogue scale (VAS) score and the Western Ontario and McMaster Universities arthritis index (WOMAC) score were observed before treatment, after treatment and in the follow-up of 12 weeks after treatment; the volume of suprapatellar bursa effusion was detected before and after treatment; the clinical efficacy was evaluated after treatment and in the follow-up in the two groups. RESULTS: After treatment and in the follow-up, the scores of clinical symptom, VAS and WOMAC were decreased compared before treatment in both groups (P<0.05), and those in the combination group were lower than the warming acupuncture group (P<0.05). After treatment, the volume of suprapatellar bursa effusion was decreased compared before treatment in both groups (P<0.05). After treatment and in the follow-up, the total effective rates were 93.3% (28/30) and 86.7% (26/30) in the combination group, which were superior to 87.1% (27/31) and 74.2% (23/31) in the warming acupuncture group respectively (P<0.05). CONCLUSION: Governor vessel moxibustion combined with warming acupuncture can improve the clinical symptoms i.e. pain and dysfunction and reduce the volume of suprapatellar bursa effusion in KOA patients with yang deficiency and cold congelation, its short-term effect and long-term effect are both superior to simple warming acupuncture.

[Warming acupuncture combined with moxibustion at Yongquan (KI 1) for knee osteoarthritis with kidney-marrow deficiency: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect between warming acupuncture combined with moxibustion at Yongquan (KI 1) and simple warming acupuncture for knee osteoarthritis with kidney-marrow deficiency. METHODS: A total of 66 patients of knee osteoarthritis with kidney-marrow deficiency were randomized into an observation group and a control group, 33 cases in each one. Warming acupuncture was applied at Neixiyan (EX-LE 4), Dubi (ST 35), Zusanli (ST 36) and Xuanzhong (GB 39) on the affected side in both of the groups. In the observation group, mild moxibustion at bilateral Yongquan (KI 1) was adopted additionally. Each treatment lasted for 30 min, 3 times a week (once every other day), and the consecutive 6 weeks of treatment were required. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (such as joint pain, stiffness and physical function), the amount of joint effusion and the serum contents of interleukin-1ß(IL-1ß), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) were observed before and after treatment in the two groups. RESULTS: The total effective rate in the observation group was 93.3% (28/30), which was superior to 87.1% (27/30) in the control group (P<0.05). Compared before treatment, the pain scores, stiffness scores, physical function scores, the amount of joint effusion and the contents of IL-1ß, TNF-α and hs-CRP after treatment were significantly reduced in the two groups (P<0.05), and the improvements of these indices in the observation group were superior to the control group (P<0.05). CONCLUSION: Warming acupuncture combined with moxibustion at Yongquan (KI 1) can improve joint function, reduce the amount of joint effusion and the contents of inflammatory response indices for knee osteoarthritis with kidney-marrow deficiency. The therapeutic effect of warming acupuncture combined with moxibustion at Yongquan (KI 1) is better than simple warming acupuncture.

Development and Internal Validation of a Prediction Model to Estimate the Probability of Left-Ventricular Diastolic Dysfunction in Stable Maintenance Hemodialysis Patients without Clinical Heart Failure.

OBJECTIVE: To develop and internally validate a multivariable prediction model based on simple clinical record data and laboratory tests and to estimate the probability of left-ventricular diastolic dysfunction (LVDD) in stable maintenance hemodialysis (MHD) patients without clinical heart failure. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: In all, 181 patients on MHD without clinical heart failure were eligible from the dialysis center of Tongren Hospital, Shanghai Jiao Tong University School of Medicine between October 2017 and September 2018. OUTCOMES: LVDD detected by echocardiography. MEASUREMENTS: We performed multivariable logistic regression using demographic, clinical, and laboratory data to identify predictors of LVDD with internal validation by using 200 bootstrap replications. RESULTS: Overall, 78 out of 181 (43.1%) patients were affected by LVDD. Predictors included in the LVDD Model were high-sensitive cardiac troponin T (OR 5.91 per 1-ln unit; 95% CI 2.17-16.13), B-type natriuretic peptide (OR 2.35 per 1-ln unit; 95% CI 1.14-4.86), and dialysis vintage (OR 1.04 per 1-month; 95% CI 1.01-1.07). The area (AUC) under the receiver operating characteristic curve of the Model was 0.871 (95% CI 0.811-0.932, p < 0.001). The calibration plot showed good agreement between predicted and observed probabilities with a calibration slope of 1.023 and intercept of -0.010. After internal validation, the Model maintained excellent discrimination (AUC 0.858, 95% CI 0.798-0.919) and good calibration (slope of 1.079, 95% CI 1.058-1.097 and intercept of -0.120, 95% CI -0.142 to -0.093). LVDD Model <0.23 can be used to rule out (sensitivity = 87.3%, negative likelihood ratio = 12.7%) and ≥0.44 can be used to rule in (specificity = 87.6%, positive likelihood ratio = 12.4%) echocardiography diagnosed LVDD. LIMITATION: External validation of the Model will be required. CONCLUSIONS: A model using routinely available simple clinical record data and laboratory tests can accurately predict the risk of LVDD in stable MHD patients. The Model and its cutoff values may be useful for early diagnosis and intervention of LVDD.

EA15, MIR22, LINC00472 as diagnostic markers for diabetic kidney disease.

This study aimed to investigate the molecular mechanisms of diabetic kidney disease (DKD) and to explore new potential therapeutic strategies and biomarkers for DKD. First we analyzed the differentially expressed changes between patients with DKD and the control group using the chip data in Gene Expression Omnibus (GEO) database. Then the gene chip was subjected to be annotated again, so as to screen long noncoding RNAs (lncRNAs) and study expression differences of these lncRNAs in DKD and controlled samples. At last, the function of the differential lncRNAs was analyzed. A total of 252 lncRNAs were identified, and 14 were differentially expressed. In addition, there were 1,629 differentially expressed messenger RNAs (mRNAs) genes, and proliferation and apoptosis adapter protein 15 (PEA15), MIR22, and long intergenic nonprotein coding RNA 472 ( LINC00472) were significantly differentially expressed in DKD samples. Through functional analysis of the encoding genes coexpressed by the three lncRNAs, we found these genes were mainly enriched in type 1 diabetes and autoimmune thyroid disease pathways, whereas in Gene Ontology (GO) function classification, they were also mainly enriched in the immune response, type I interferon signaling pathways, interferon-γ mediated signaling pathways, and so forth. To summary, we identified EA15, MIR22, and LINC00472 may serve as the potential diagnostic markers of DKD.

High-sensitive cardiac troponin T: a biomarker of left-ventricular diastolic dysfunction in hemodialysis patients.

OBJECTIVE: To identify the relationship between serum high-sensitive cardiac troponin T (hs-cTnT) and left ventricular diastolic dysfunction (LVDD) among maintenance hemodialysis patients and to further explore the value of hs-cTnT in evaluating and predicting LVDD in this special group of patients. METHODS: In a cross-sectional study, 152 dialysis patients with end-stage renal disease (ESRD) underwent Hs-cTnT measurement using the high sensitivity assay. Echocardiography measurements were carried out according to the American Society of Echocardiography recommendations and E/E' > 15 or E' < 7 cm/s was defined as diastolic dysfunction. Demographic, biochemical, and echocardiographic values of left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), left atrial diameter, early/late peak velocities ratio (E/A), early peak diastolic annular velocity (E') and E/E' were compared across quartiles of hs-cTnT. The association of plasma hs-cTnT concentrations with echocardiographic parameters was analyzed by Spearman's correlation. The relationship between serum hs-cTnT and LVDD parameters of E/E' and E' was analyzed using multivariate regression analysis, and the value of hs-cTnT on assessing LVDD was evaluated by receiver-operating characteristic (ROC) curves. RESULTS: The median value of hs-cTnT was 45 pg/ml (range 28-73). All patients had detectable hs-cTnT, while 88% had greater hs-cTnT than the 99th percentile of the general population (14 pg/ml). Serum hs-cTnT values showed a significantly positive correlation with E/E' (r = 0.739, p < 0.001) and LVMI (r = 0.608, p < 0.001), but showed a negative correlation with E' (r = - 0.554, p < 0.001). Serum hs-cTnT was not associated with LV systolic dysfunction. The associations of hs-cTnT with E/E' and E' persisted after multivariate adjustment for LVMI and comorbidities. In logistic multiple regression analysis, compared with the lowest quartile of hs-cTnT, the highest two quartiles were approximately 5 and 11 times more likely to have E/E' > 15 and 7 and 17 times more likely to have E' < 7 cm/s. The area under the ROC curve for hs-cTnT evaluating E/E' > 15 was 0.847 and evaluating E' < 7 cm/s was 0.799, which denoted a moderate accuracy. CONCLUSIONS: Our studies suggest that serum hs-cTnT may serve as a biomarker of LVDD in hemodialysis patients.

Specific expression network analysis of diabetic nephropathy kidney tissue revealed key methylated sites.

Diabetic nephropathy (DN) is one of the most common and serious complication in diabetes patients. However, the evidences of gene regulation mechanism and epigenetic modification with DN remain unclear. Therefore, it is necessary to search regulating genes for early diagnosis on DN. We identified tissue specific genes through mining the gene expression omnibus (GEO) public database, enriched function by gene ontology (GO), and kyoto encyclopedia of genes and genomes (KEGG) analysis, and further compared tissue-specific network. Meanwhile, combining with differentially methylated sites, we explored the association epigenetic modification with the pathogenesis of DN. Glomeruli (Glom) may be the main tissue of signal recognition and tubulointerstitium (Tub) is mainly associated with energy metabolism in the occurrence of DN. By comparing tissue-specific networks between Glom and Tub, we screened 319 genes, which played an important role in multiple tissue on kidney. Among them, ANXA2, UBE2L6, MME, IQGAP, SLC7A7, and PLG played a key role in regulating the incidence of DN. Besides, we also identified 1 up-regulated gene (PIK3C2B) and 39 down-regulated genes (POLR2G, DDB1, and ZNF230, etc.) in the methylated data of Glom specific genes. In the Tub specific expressed genes, we identified two hypo-methylated genes (PPARA and GLS). Tub mainly caused abnormal energy metabolism, and Glom caused the changes in cell connections and histone modification. By analyzing differentially methylated sites and tissue-specific expressed genes, we found the change of methylated status about the core regulating genes may be a potential factor in the pathogenesis of DN.

[Effect of joss stick moxibustion combined with pricking and cupping for acute herpes zoster and its mechanism of analgesia].

OBJECTIVE: To observe the effects of conventional western medication and joss stick moxibustion combined with pricking and cupping for herpes zoster in acute stage, and to explore its analgesic mechanism. METHODS: Seventy patients with acute herpes zoster were randomized into an observation group (33 cases after 2 dropping) and a control group (34 cases after 1 dropping). Patients in the observation group were treated with joss stick moxibustion combined with pricking and cupping at local ashi points for 7 times, once every other day. Oral acyclovir, vitamin B1 and mecobalamin tablets were applied in the control group for continuous 14 days, and interferon injection was used for continuous 6 days, etc. The herpes evaluation indexes of blister stopping time, scab time and decrustation time as well as pain intensity were observed before and after treatment. Peripheral serum substance P (SP) content of herpes local situation was detected. The comprehensive effects were evaluated. RESULTS: The blister stopping time, scab time and decrustation time in the observation group were shorter than those in the control group (all P<0.05). There was no statistical significance for pain relief degree between the two groups (P>0.05). The pain beginning to ease time and duration time in the observation group were better than those in the control group (both P<0.05). The contents of SP in the two groups decreased after treatment (both P<0.01), and it was better in the observation group (P<0.05). The total effective rate of the observation group after treatment was 87.9% (29/33), and that of the control group was 85.3% (29/34), which were not statistically significant (P>0.05). The cured rate of the observation group was better than that of the control group [66.7% (22/33) vs 58.8% (20/34), P<0.05]. CONCLUSION: Joss stick moxibustion combined with pricking and cupping are effective for herpes zoster, which have quicker and good analgesic effects than conventional western medication. Its mechanism may be related to reducing the content of SP more fast and to a larger degree.

Soluble monosodium urate, but not its crystal, induces toll like receptor 4-dependent immune activation in renal mesangial cells.

BACKGROUND: Uric acid has emerged as a novel and potential modifiable risk factor for the incidence and progression of kidney diseases, however, the deteriorate effect of uric acid on renal mesangial cells remains unclear. The present study is to examine the immune activation of soluble and crystal forms of uric acid in human mesangial cells. METHODS: We stimulated primary human mesangial cells (HMCs) with increasing concentrations (from 50 to 200 µg/ml) of soluble monosodium urate (MSU) or MSU crystals. We examined interleukin (IL)-1ß protein expression levels in cell culture by ELISA. The stimulated HMCs were further stimulated with soluble MSU or MSU crystals at 200 µg/ml with or without the pre-incubation of toll like receptor (TLR) 4 inhibitor TAK242 (1µM). TLR4, nod-like receptor protein (NLRP3, also known as NALP3), IL-1ß, human leukocyte antigen (HLA)-DR and CD40 were examined by Realtime-PCR, Western blot and ELISA, respectively. RESULTS: We found that both soluble MSU and MSU crystals increased IL-1ß protein expression levels in dose-dependent fashion. Soluble MSU significantly enhanced the expression of TLR4, NLRP3, IL-1ß, HLA-DR and CD40 while MSU crystals only upregulated the expression of TLR4 and IL-1ß. TLR4 inhibitor TAK242 significantly blocked the up-regulation of NLRP3, IL-1ß, HLA-DR and CD40 induced by soluble MSU while no TAK242 suppression effect on MSU crystals induced IL-1ß up-regulation was found. CONCLUSIONS: Our results suggested that soluble MSU, but not MSU crystals, induce NLRP3, IL-1ß, HLA-DR and CD40 upregulation in a TLR4-dependent manner. These findings indicate that soluble MSU may play a pathological role in hyperuricemia induced renal mesangial injury.