Comprehensive Analysis of PKD1 and PKD2 by Long-Read Sequencing in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by heterogeneous variants in the PKD1 and PKD2 genes. Genetic analysis of PKD1 has been challenging due to homology with 6 PKD1 pseudogenes and high GC content. METHODS: A single-tube multiplex long-range-PCR and long-read sequencing-based assay termed "comprehensive analysis of ADPKD" (CAPKD) was developed and evaluated in 170 unrelated patients by comparing to control methods including next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification. RESULTS: CAPKD achieved highly specific analysis of PKD1 with a residual noise ratio of 0.05% for the 6 pseudogenes combined. CAPKD identified PKD1 and PKD2 variants (ranging from variants of uncertain significance to pathogenic) in 160 out of the 170 patients, including 151 single-nucleotide variants (SNVs) and insertion-deletion variants (indels), 6 large deletions, and one large duplication. Compared to NGS, CAPKD additionally identified 2 PKD1 variants (c.78_96dup and c.10729_10732dup). Overall, CAPKD increased the rate of variant detection from 92.9% (158/170) to 94.1% (160/170), and the rate of diagnosis with pathogenic or likely pathogenic variants from 82.4% (140/170) to 83.5% (142/170). CAPKD also directly determined the cis-/trans-configurations in 11 samples with 2 or 3 SNVs/indels, and the breakpoints of 6 large deletions and one large duplication, including 2 breakpoints in the intron 21 AG-repeat of PKD1, which could only be correctly characterized by aligning to T2T-CHM13. CONCLUSIONS: CAPKD represents a comprehensive and specific assay toward full characterization of PKD1 and PKD2 variants, and improves the genetic diagnosis for ADPKD.

Inflammation Is More Sensitive than Cell Proliferation in Response to Rapamycin Treatment in Polycystic Kidney Disease.

INTRODUCTION: It has been reported that rapamycin inhibited inflammation in renal interstitial diseases. We therefore hypothesized that rapamycin could attenuate inflammation in polycystic kidney disease (PKD). METHODS: Han:SPRD rats were treated with rapamycin by daily gavage from 4 weeks to 12 weeks of age at the dosage of 0.5 mg/kg/day (low dose) or 1 mg/kg/day (high dose). WT9-12 human PKD cells were treated with various concentrations of rapamycin. RESULTS: Two-kidney/total body weight ratio and cystic index in Cy/+ kidneys were significantly reduced with the treatment of low-dose rapamycin and further reduced by the treatment with high-dose rapamycin. However, the renal function of Cy/+ rats was equally improved by the treatment with either low-dose or high-dose rapamycin. The renal cell proliferation was significantly decreased in Cy/+ kidneys with the treatment of low-dose rapamycin and was further decreased with the treatment of high-dose rapamycin as examined by Ki67 staining. The phosphorylation of S6K in cystic kidneys was decreased by low-dose rapamycin and further decreased by high-dose rapamycin. Both low-dose and high-dose rapamycin treatment decreased macrophage infiltration and the expression of complement factor B (CFB), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α) to a similar level. The expression of CFB, MCP-1, and TNF-α and phosphorylation of S6K were inhibited in WT9-12 cells treated with 10 nm rapamycin at 24 h and 48 h, respectively. Moreover, the phosphorylation of Akt was not increased by 1 nm and 10 nm of rapamycin and enhanced by 1 µm rapamycin treatment. Interestingly, WT9-12 cell proliferation could be inhibited by 1 µm rapamycin. CONCLUSION: Low dose of rapamycin could inhibit inflammation and protect renal function in PKD. Inflammation is more sensitive than cell proliferation in response to rapamycin treatment in PKD.

Susceptibility of renal fibrosis in diabetes: Role of hypoxia inducible factor-1.

Diabetes may prevent kidney repair and sensitize the kidney to fibrosis or scar formation. To test this possibility, we examined renal fibrosis induced by unilateral ureteral obstruction (UUO) in diabetic mouse models. Indeed, UUO induced significantly more renal fibrosis in both Akita and STZ-induced diabetic mice than in nondiabetic mice. The diabetic mice also had more apoptosis and interstitial macrophage infiltration during UUO. In vitro, hypoxia induced higher expression of the fibrosis marker protein fibronectin in high glucose-conditioned renal tubular cells than in normal glucose cells. Mechanistically, hypoxia induced significantly more hypoxia-inducible factor-1 α (HIF-1 α) in high glucose cells than in normal glucose cells. Inhibition of HIF-1 attenuated the expression of fibronectin induced by hypoxia in high-glucose cells. Consistently, UUO induced significantly higher HIF-1α expression along with fibrosis in diabetic mice kidneys than in nondiabetic kidneys. The increased expression of fibrosis induced by UUO in diabetic mice was diminished in proximal tubule-HIF-1α-knockout mice. Together, these results indicate that diabetes sensitizes kidney tissues and cells to fibrogenesis probably by enhancing HIF-1 activation.

Non-Iterative Multiscale Estimation for Spatial Autoregressive Geographically Weighted Regression Models.

Multiscale estimation for geographically weighted regression (GWR) and the related models has attracted much attention due to their superiority. This kind of estimation method will not only improve the accuracy of the coefficient estimators but also reveal the underlying spatial scale of each explanatory variable. However, most of the existing multiscale estimation approaches are backfitting-based iterative procedures that are very time-consuming. To alleviate the computation complexity, we propose in this paper a non-iterative multiscale estimation method and its simplified scenario for spatial autoregressive geographically weighted regression (SARGWR) models, a kind of important GWR-related model that simultaneously takes into account spatial autocorrelation in the response variable and spatial heterogeneity in the regression relationship. In the proposed multiscale estimation methods, the two-stage least-squares (2SLS) based GWR and the local-linear GWR estimators of the regression coefficients with a shrunk bandwidth size are respectively taken to be the initial estimators to obtain the final multiscale estimators of the coefficients without iteration. A simulation study is conducted to assess the performance of the proposed multiscale estimation methods, and the results show that the proposed methods are much more efficient than the backfitting-based estimation procedure. In addition, the proposed methods can also yield accurate coefficient estimators and such variable-specific optimal bandwidth sizes that correctly reflect the underlying spatial scales of the explanatory variables. A real-life example is further provided to demonstrate the applicability of the proposed multiscale estimation methods.

Xper computed tomography-guided translumbar inferior vena cava catheterization for long-term hemodialysis: A case report and literature review.

Hemodialysis is the most widely used renal replacement therapy for end-stage renal disease patients. Exhausted vascular access due to repeated indwelling central venous catheters is becoming a challenging clinical problem, which also contributes to reduced survival of the hemodialysis patients. Lack of conventional peripheral and central venous access mandates the use of alternative strategies. We present a case of translumbar dialysis catheter (TLDC) for long-term hemodialysis in a patient with central venous occlusion refractory to conventional endovascular techniques. After a careful literature review, totally 10 cohort studies including 216 cases through TLDC were reported. The incidence of procedure-related complications was very low. The catheter-related infection rate of TLDC was comparable with overall tunneled cuffed catheters (TCCs) reported by clinical practice guidelines for vascular access. Although the patency might be relatively low due to the catheter-related complications, TLDC could be rescued by multiple systemic and topical medications and interventional therapies. Percutaneous translumbar placement of a cuffed tunneled hemodialysis catheter directly into the inferior vena cava (IVC) can provide a relatively safe salvage when traditional central venous sites such as the internal jugular, femoral, subclavian veins are unavailable. Xper computed tomography together with real-time fluoroscopic guidance can reduce the intraoperative risks and complications.

Comparison of Outcomes between Percutaneous and Surgical Placement of Peritoneal Dialysis Catheters in Uremic Patients: A Meta-Analysis.

BACKGROUND: The optimal technique for inserting peritoneal dialysis catheters in uremic patients remains debated. This meta-analysis aimed to summarize the current evidence evaluating the efficacy and safety of percutaneous insertion methods compared to surgical methods. METHOD: A literature search was performed in the PubMed, EMBASE, Cochrane, and Web of Science databases. The primary outcome was defined as catheter survival. The secondary outcomes were mechanical and infectious complications related to catheter insertion. RESULTS: Twenty studies were finally identified, including 2 randomized controlled trials. The pooled results of catheter survival, overall mechanical complications, and infectious complications were not significant (odds ratio [OR] = 1.10, 95% confidence interval (CI) = 0.76-1.57, p = 0.62; OR = 0.73, 95% CI = 0.48-1.11, p = 0.14; and OR = 0.64, 95% CI = 0.37-1.09, p = 0.14, respectively). Comparison stratified by the blind percutaneous method versus open surgery indicated a lower overall number of mechanical complications (OR = 0.54, 95% CI = 0.31-0.93, I2 = 72%) and malposition rate (OR = 0.56, 95% CI = 0.34-0.90, I2 = 0%). The leakage rate was higher in the blind percutaneous group than in the open surgery group (OR = 2.55, 95% CI = 1.72-3.79, I2 = 0%); the guided percutaneous method achieved a similar leakage risk to the surgical methods. CONCLUSIONS: The blind percutaneous method performed better with fewer overall mechanical complications and less malposition than open surgery. The leakage risk was higher in the blind percutaneous group, while the guided percutaneous placement group showed similar outcomes to the surgical method groups. Percutaneous methods also had a lower infection risk, which needs further evidence to be confirmed.

Thrombotic thrombocytopenic purpura developed after pegylated interferon treatment for hepatitis B infection.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia. It is related to severe deficiency in ADAMTS13, which is usually acquired via ADAMTS13 autoantibodies or inherited via mutations of the ADAMTS13 gene. The etiology of acquired TTP including HIV infection, pregnancy, autoimmune disease, organ transplantation, drugs, malignancy and so on. Here, we firstly reported a patient diagnosed as acquired TTP after pegylated interferon therapy for hepatitis B and COVID-19 vaccination. CASE PRESENTATION: A 36-year-old male attended to our unit with a five-day history of intermittent hematuria and progressive fatigue on January 5th, 2022. He had a 13 years history of hepatitis B infection and undergone pegylated interferon treatment (which was paused for two months because of COVID-19 vaccination) for nearly 3 years. Laboratory evaluation revealed a haemoglobin level of 61 g/L, platelet count of 11 × 109/L, lactate dehydrogenase 2133 U/L. The direct and indirect Coombs test were both negative. On a peripheral blood smear, there were about 18.8% schistocytes. Meanwhile, the results of ADAMTS 13 activity and antibody were < 5% and 181.34 ng/ml (131.25-646.5), respectively CONCLUSION: This case firstly reported the rare complication of TTP after pegylated interferon treatment for hepatitis B and COVID-19 vaccine injection. This unique sign warrants more attention as an early cue of diagnosis of TTP and be aware of the rarity adverse effect of interferon therapy and COVID-19 vaccination.

NS398 as a potential drug for autosomal-dominant polycystic kidney disease: Analysis using bioinformatics, and zebrafish and mouse models.

Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by uncontrolled renal cyst formation, and few treatment options are available. There are many parallels between ADPKD and clear-cell renal cell carcinoma (ccRCC); however, few studies have addressed the mechanisms linking them. In this study, we aimed to investigate their convergences and divergences based on bioinformatics and explore the potential of compounds commonly used in cancer research to be repurposed for ADPKD. We analysed gene expression datasets of ADPKD and ccRCC to identify the common and disease-specific differentially expressed genes (DEGs). We then mapped them to the Connectivity Map database to identify small molecular compounds with therapeutic potential. A total of 117 significant DEGs were identified, and enrichment analyses results revealed that they are mainly enriched in arachidonic acid metabolism, p53 signalling pathway and metabolic pathways. In addition, 127 ccRCC-specific up-regulated genes were identified as related to the survival of patients with cancer. We focused on the compound NS398 as it targeted DEGs and found that it inhibited the proliferation of Pkd1-/- and 786-0 cells. Furthermore, its administration curbed cystogenesis in Pkd2 zebrafish and early-onset Pkd1-deficient mouse models. In conclusion, NS398 is a potential therapeutic agent for ADPKD.

The role of the complement factor B-arginase-polyamine molecular axis in uremia-induced cardiac remodeling in mice.

The role of complement system in heart diseases is controversial. Besides, the mechanisms by which complement components participate in cardiac remodeling (CR) and heart failure during uremia are unclear. In this study, 5/6 nephrectomy was performed to adult mice to establish the uremic model and CR deteriorated over the course of uremia. Although complement pathways were not further activated over the course of the disease, soluble complement factor B (CFB) was upregulated at post-nephrectomy day 90 (PNx90) compared with PNx30. Further, CFB notably deteriorated CR in uremic mice but this effect was reversed by depletion of macrophages with liposomal clodronate. In vivo and in vitro CFB upregulated arginase 1 (ARG1) expression, increased ARG1 enzymatic activity, and stimulated the syntheses of ornithine, leading to polyamine overproduction in macrophages. Putrescine, an important polyamine, promoted cardiac fibroblast proliferation and collagen production, resulting in progressive CR. In vivo the inhibition of ARG1 activity with Nω -hydroxyl-l-arginine remarkably improved the general survival rates, inhibited the infiltration of cardiac fibroblasts, and alleviated progression of CR in uremic mice. Taken together, the CFB-ARG1-putrescine axis is related to progression of CR and ARG1 hyperactivity in macrophages may provide a novel therapeutic target against the heart injury in uremia.

Association between serum advanced oxidation protein products and mortality risk in maintenance hemodialysis patients.

BACKGROUND: The association between serum advanced oxidation protein products (AOPP) and mortality risk remains equivocal. We aimed to assess the correlation of serum AOPP levels with the risk of all-cause mortality in hemodialysis (HD) patients. METHODS: A total of 1394 maintenance HD patients with complete data on AOPP and related parameters were included from China Collaborative Study on Dialysis (CCSD), a multi-center, prospective cohort study. The primary outcome was all-cause mortality, the secondary outcome was cardiovascular disease (CVD) mortality. RESULTS: During a median follow-up duration of 5.2 years (IQR, 2.1-5.4), all-cause mortality occurred in 492 (31.4%) participants. Overall, there was a reversed L-shaped association between serum AOPP and all-cause mortality in HD patients (P for nonlinearity = 0.04), with an inflection point at 87 µmol/L. Accordingly, there was no significant association between serum AOPP and all-cause mortality (per SD increment; HR, 0.94; 95%CI, 0.84, 1.05) in participants with AOPP < 87 µmol/L. However, there was a positive relationship of serum AOPP and all-cause mortality (per SD increment; HR, 1.24; 95%CI, 1.08, 1.42) in those with AOPP ≥ 87 µmol/L. Moreover, a similar trend was found for CVD mortality. CONCLUSIONS: Elevated serum AOPP levels were associated with higher risk of all-cause mortality in Chinese maintenance HD patients.

PKD2 gene variants in Chinese patients with autosomal dominant polycystic kidney disease.

PKD2 gene variants account for 4.5% to 20% of patients with autosomal dominant polycystic kidney disease (ADPKD). Little is known about the clinical characteristics of PKD2 variants in Chinese patients with ADPKD. Herein, we performed a comprehensive search for variants of PKD2 gene in 44 Chinese ADPKD pedigrees and a total of 37 variants were identified. Of these 37 variants, 18 were nonsense variants, 10 frameshift variants, 4 missense variants, and 5 splice site variants. 11/37 variants were detected for the first time. The median age at diagnosis was 30.5 years, and positive family history was detected in 77.27% patients, liver cysts in 68.18%, hypertension in 45.45%, nephrolithiasis in 31.82%, macro-hematuria in 22.73%, and proteinuria in 13.63%. The level of estimated glomerular filtration rate in 8/39 patients were blow 60 ml/min/1.73m2 . 11/17 patients were classified as rapid progression by Mayo Clinic classification. The end stage renal disease (ESRD) events were reported in 9/22 pedigrees, and the presence of nephrolithiasis and macro-hematuria were significantly associated with ESRD in the pedigrees with PKD2 variants. The identified variants and clinical features will facilitate the early diagnosis and prognosis prediction in Chinese ADPKD patients with PKD2 variants.

Serum and Tissue Levels of Advanced Glycation End Products and Risk of Mortality in Patients on Maintenance Hemodialysis.

BACKGROUND: The relation of tissue and circulating advanced glycation end products (AGEs) with mortality in hemodialysis (HD) patients remains inconclusive. We aimed to investigate the association of serum AGEs (CML) and tissue AGEs estimated by skin autofluorescence (SAF) with all-cause and cardiovascular disease (CVD) mortality, and examine the possible modifiers for the association in HD patients with by far the largest sample size in any similar studies. METHODS: A total of 1,634 HD patients were included from the China Cooperative Study on Dialysis (CCSD), a multicenter prospective cohort study. The primary and secondary outcomes were all-cause mortality and CVD mortality, respectively. RESULTS: The median follow-up duration was 5.2 years. Overall, there was a positive relation of baseline SAF levels with the risk of all-cause mortality (per 1 AU increment, adjusted hazard ratio (HR), 1.30; 95% confidence interval (CI): 1.12, 1.50) and CVD mortality (per 1 AU increment, adjusted HR, 1.36; 95% CI: 1.14, 1.62). Moreover, a stronger positive association between baseline SAF (per 1 AU increment) and all-cause mortality was found in participants with shorter dialysis vintage, or lower C-reactive protein levels (Both p interactions <0.05). Nevertheless, there was no significant association between serum CML and the risk of mortality. CONCLUSIONS: In patients undergoing long-term HD, baseline SAF, but not serum CML, was significantly associated with the risk of all-cause and CVD death.

Hyperoxalemia Leads to Oxidative Stress in Endothelial Cells and Mice with Chronic Kidney Disease.

INTRODUCTION: Cardiovascular disease is the most common cause of morbidity and mortality in patients with ESRD. In addition to phosphate overload, oxalate, a common uremic toxin, is also involved in vascular calcification in patients with ESRD. The present study investigated the role and mechanism of hyperoxalemia in vascular calcification in mice with uremia. METHODS: A uremic atherosclerosis (UA) model was established by left renal excision and right renal electrocoagulation in apoE-/- mice to investigate the relationship between oxalate loading and vascular calcification. After 12 weeks, serum and vascular levels of oxalate, vascular calcification, inflammatory factors (TNF-α and IL-6), oxidative stress markers (malondialdehyde [MDA], and advanced oxidation protein products [AOPP]) were assessed in UA mice. The oral oxalate-degrading microbe Oxalobacter formigenes (O. formigenes) was used to evaluate the effect of a reduction in oxalate levels on vascular calcification. The mechanism underlying the effect of oxalate loading on vascular calcification was assessed in cultured human aortic endothelial cells (HAECs) and human aortic smooth muscle cells (HASMCs). RESULTS: Serum oxalate levels were significantly increased in UA mice. Compared to the control mice, UA mice developed more areas of aortic calcification and showed significant increases in aortic oxalate levels and serum levels of oxidative stress markers and inflammatory factors. The correlation analysis showed that serum oxalate levels were positively correlated with the vascular oxalate levels and serum MDA, AOPP, and TNF-α levels, and negatively correlated with superoxide dismutase activity. The O. formigenes intervention decreased serum and vascular oxalate levels, while did not improve vascular calcification significantly. In addition, systemic inflammation and oxidative stress were also improved in the O. formigenes group. In vitro, high concentrations of oxalate dose-dependently increased oxidative stress and inflammatory factor expression in HAECs, but not in HASMCs. CONCLUSIONS: Our results indicated that hyperoxalemia led to the systemic inflammation and the activation of oxidative stress. The reduction in oxalate levels by O. formigenes might be a promising treatment for the prevention of oxalate deposition in calcified areas of patients with ESRD.

Leflunomide plus low-dose prednisone in patients with progressive IgA nephropathy: a multicenter, prospective, randomized, open-labeled, and controlled trial.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common cause of glomerulonephritis worldwide, and the optimal approach to its treatment remains a significant challenge. METHODS: We did a prospective, randomized, open-labeled, multicenter, controlled trial, comprised of 3-month run-in, 12-month treatment, and 12-month follow-up phases. After 3-month run-in phase, patients with biopsy-confirmed IgAN at risk of progression were randomly allocated to LEF plus low-dose prednisone (LEF + prednisone group) or conventionally accepted-dose prednisone [prednisone(alone) group] Our primary outcome was 24-h urine protein excretion (UPE) and secondary outcomes were serum albumin (sALB), serum creatinine (Scr), and eGFR. Safety was evaluated in all patients who received the trial medications. RESULTS: One hundred and eight patients [59 in LEF + prednisone group, 49 in prednisone (alone) group]were enrolled and finished their treatment and follow-up periods. There is no significant difference in the baseline level between the two groups. Compared with baseline, both groups showed a significant decrease in 24-h UPE (p < 0.01) and increase in sALB (p < 0.01), with stable Scr and eGFR throughout the 12-month treatment period. What's more, these effects were sustained through the 12-month follow-up period. However, there was no difference in 24-h UPE, sALB, Scr, and eGFR between the two groups (p > 0.05). At 12 months, a difference in overall response rate, relapsing rate, and incidence of adverse events between the two groups was not significant. CONCLUSIONS: The efficacy and safety of LEF plus low-dose prednisone and conventionally accepted-dose prednisone in the treatment of progressive IgAN are comparable.

Matrix metalloproteinase-7 in platelet-activated macrophages accounts for cardiac remodeling in uremic mice.

Heart failure is the leading cause of mortality in patients with end-stage renal disease, and progressive cardiac remodeling is the key pathological basis of heart failure. However, the mechanism by which uremia-induced cardiac remodeling occurs is not well understood. Here, we showed that platelets were significantly activated in 5/6 nephrectomy-operated mice, and cardiac remodeling in the uremic mice was significantly improved when platelets were effectively depleted. A cardiac fibrosis-related gene expression profile revealed that Mmp7, encoding matrix metalloproteinase-7 (MMP-7), exhibited the greatest degree of downregulation in the hearts of uremic mice with platelets depleted. Using fluorescence-activated cell sorting, we discovered that MMP-7 was mainly expressed in M1 and M4 cardiac macrophages, although it was also extensively expressed in heart tissues. For the upstream therapeutic target, neutralization of platelet factor 4 (PF4) with monoclonal antibody not only significantly suppressed M4 macrophages in vivo, but also notably prevented collagen destruction in heart tissues. For the downstream therapeutic target, the pharmacological inhibition of MMP-7 with selective inhibitor failed to notably affect the platelet status, but significantly reduced heart collagen destruction in mice, a further indication that MMP-7 is a crucial downstream molecular target of platelet activation. In vitro, platelets interacted with macrophages and drove them to upregulate MMP-7 expression via free molecules, especially PF4. Taken together, the data suggest that MMP-7 is a key downstream target of platelet activation during uremia. Thus, MMP-7 is a likely and novel therapeutic target for intervention of cardiac remodeling during uremia.

A Sphingosine-1-Phosphate Modulator Ameliorates Polycystic Kidney Disease in Han:SPRD Rats.

BACKGROUND: Inflammation plays an important role in polycystic kidney disease (PKD). Cordyceps sinensis, a prized -Chinese medicinal herb, exerts anti-tumor, anti-inflammatory and anti-metastatic effects and benefits patients with kidney diseases. The aim of this study was to test the efficacy of FTY720, an immunosuppressant derived from C. sinensis, in a rat cystic kidney disease model, and explore its underlining mechanism. METHODS: Male wild type and Cy/+ Han:SPRD rats were treated with FTY720 at 3 and 10 mg/kg/day for 5 weeks and 12 weeks by gavage. Blood and kidney were collected for functional, morphological, RNA, and protein analysis. RESULTS: Inflammation is activated in Cy/+ Han:SPRD rats. Inflammatory cytokines including interleukin 6 and tumor necrosis factor alpha were upregulated and inflammation-related pathways were activated, such as nuclear factor κB and signal transducer and activator of transcription 3 (STAT3) pathways. Furthermore, the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), a regulator of inflammation, was accumulated in the Cy/+ Han:SPRD rats. FTY720 significantly reduced cyst growth and delayed disease progression by reducing the accumulation of S1P, thereby inhibiting inflammatory responses. CONCLUSION: FTY720 treatment reduced the expression of inflammatory cytokines and attenuated the activation of NK-κB and STAT3 pathways in Cy/+ Han:SPRD rats. It suggests that FTY720 may serve as a therapeutic agent for clinical autosomal dominant PKD treatment.

New-onset glucose disorders in peritoneal dialysis patients: a meta-analysis and systematic review.

BACKGROUND: Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. METHODS: We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. RESULTS: We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) was 8% [95% confidence interval (CI) 4-12; I2 = 98%] adjusted by sample sizes in PD patients. Pooled incidence rates of new-onset IGT and IFG were 15% (95% CI 3-31; I2 = 97%) and 32% (95% CI 27-37), respectively. There was no significant difference in NODM risk between PD and HD [risk ratio 0.99 (95% CI 0.69-1.40); P = 0.94; I2 = 92%]. PD patients with NODM were associated with an increased risk of mortality [hazard ratio 1.06 (95% CI 1.01-1.44); P < 0.001; I2 = 92.5%] compared with non-DM PD patients. CONCLUSIONS: Around half of PD patients may develop a glucose disorder, which can affect the prognosis by significantly increasing mortality. The incidence did not differ among different ethnicities or between PD and HD. The risk factor analysis did not draw a definitive conclusion. The glucose tolerance test should be routinely performed in PD patients.

A 64-year-old woman with raccoon eyes following kidney biopsy: a case report.

BACKGROUND: Raccoon eyes or periorbital ecchymosis is caused by blood tracking into periorbital tissues, which is mostly recognized in injuries of head and neck, basal skull fractures, convexity fractures and facial fractures. It was also reported in systematic disorders, such as multiple myeloma, amyloidosis, Kaposi's sarcoma, migraine and neuroblastoma. However, it is unusual to see a patient showing periorbital purpura after kidney biopsy with no other ecchymosis. Here, we firstly reported this rare symptom after kidney biopsy in a patient who was finally diagnosed as immunoglobulin light chain (AL) amyloidosis. CASE PRESENTATION: A 64-year old woman was admitted to our clinic with 1.5 years history of sub-nephrotic proteinuria and slowly progressive deterioration of renal function. Laboratory -investigations revealed an M-peak in the λ fraction of IgA and concentrations of serum free-light-chain (FLC) were 44.95 mg/L for κ isotype and 173 mg/L for λ isotype. Unexpectedly the patient showed periorbital purpura 24 h later after kidney biopsy with no more other ecchymosis. Renal biopsy showed massively glomerulosclerosis, interstitial fibrosis with positively Congo red staining in mesangial areas. For fluorescent staining, the kidney tissue showed strongly λ light-chain deposition. The fibrils (8-12 nm in diameter) were confirmed by electron micrograph. CONCLUSIONS: This case firstly reported this rare symptom after the kidney biopsy in a patient who was finally diagnosed as AL amyloidosis. And this unique sign of periorbital ecchymosis warrants more attention as an early cue of amyloidosis.

The fertility willingness and acceptability of preimplantation genetic testing in Chinese patients with autosomal dominant polycystic kidney disease.

BACKGROUND: With the development and progression of genetic technology, preimplantation genetic testing (PGT) has made it possible to block the inheritance of autosomal dominant polycystic kidney disease (ADPKD) as early as possible. However, we need to know the patients' fertility intentions and their acceptance of PGT. METHODS: A questionnaire survey was conducted to collect data on the basic demographic data, quality of life, social support, fertility willingness, and level of understanding of genetic testing for blocking the inheritance of ADPKD among patients aged 18-45 years in seven hospitals from January 2018 to December 2018. After verification, statistics were calculated. RESULTS: A total of 260 patients with ADPKD were interviewed, including 137males (52.7%) and 123 females (47.3%). The overall fertility willingness rate was low (n = 117, 45.0%). The proportion of married patients aged 25-34 years that were at the optimal reproductive age but did not yet have children was relatively high (n = 77, 67.0%). The fertility intentions of ADPKD patients were significantly influenced by age (OR: 0.101, 95% CI 0.045-0.225, P < 0.001) and education level (OR: 2.134, 95% CI 1.162-3.917, P = 0.014). Among patients who are willing to have children, 207 (79.6%) of them would choose PGT technology. Among those who were not sure whether they would choose PGT technology, the first major concern was technical safety (49.2%). CONCLUSIONS: The reproductive desire of childbearing ADPKD patients in China was low. Strengthening the health education of ADPKD genetic knowledge and reducing the cost of related technologies may improve the fertility intentions and reduce the barriers to acceptance of PGT.

[Clinical practice guidelines for polycystic kidney diseases].

Polycystic kidney disease (PKD) is a group of hereditary kidney diseases caused by genetic mutations. Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are the two main forms of PKD. The pathological features of PKD include progressive enlargement of renal cysts and destruction of kidney structure, which may eventually lead to end-stage renal disease (ESRD). As a result, the lives of PKD patients can only be sustained by dialysis or kidney transplantation. On the basis of basic research, clinical studies and guidelines issued for PKD at home and abroad, and by combining with the reality of Chinese PKD patients, this guideline has summarized the key points for the genetic counseling and clinical treatment of PKD, with an aim to improve the understanding and standardized diagnosis and treatment for such disorders.