From tuberous sclerosis complex to end stage renal disease: who are these patients?
In patients with tuberous sclerosis complex (TSC), renal complications are not limited to bleeding angiomyolipoma (AML); although rare, end-stage renal disease (ESRD) may occur. New treatments (e.g., mammalian target of rapamycin (m-Tor) inhibitors) for AML might influence the epidemiology of ESRD in patients with TSC. In France, 99 patients with TSC from the Renal Epidemiology and Information Network (REIN) registry and having undergone renal replacement therapy (RRT) between 2002 and 2016 were included in the present study. Additional data were collected from the patients’ medical charts. The mean ± standard deviation age at RRT initiation was 48.4 ± 16.4 and 73.8% had a neurologic impairment. Fifty-four patients underwent kidney transplantation after an average of 23 ± 12.3 months on dialysis. Among the 61 patients with additional data the most common renal lesion was AML: 26.2% of the patients had isolated AML, and 26.2% had AML and renal cysts, 65.6% of patients had undergone nephrectomy, and 16.4% had undergone at least one embolization. None of the patients had been treated with an m-Tor inhibitor before dialysis. The graft survival rate was 92.5% at 5 years and 70.2% at 10 years.
The present cohort study is the first to have assessed TSC patients on RRT from a national registry. Nephrectomy or embolization due to AML was the leading cause of ESRD in our cohort. By reducing the size of the AML, m-tor inhibitors might lower the risk of complications and thus reduce the number of patients with TSC requiring RRT.
Effect of Bariatric Surgery on Diagnosed Chronic Kidney Disease and Cardiovascular Events in Patients with Insulin-treated Type 2 Diabetes: a Retrospective Cohort Study from a Large UK Primary Care Database.
To compare the effect of bariatric surgery on renal, chronic kidney disease (CKD) and cardiovascular (CV) outcomes among obese patients with insulin-treated type 2 diabetes (T2D) with and without microalbuminuria (i.e., uACR > 3.0 mg/mmol).A retrospective cohort study was conducted among 11,125 active patients with T2D from The Health Improvement Network (THIN) database. Propensity score matching (up to 1:6 ratio) was used to identify patients who underwent bariatric surgery (N = 131) with a non-bariatric cohort (N = 579). Follow-up was undertaken for 10 years (6487 person-years) to compare differences in risk of cardiovascular events and in renal outcomes.
RESULTS
For the matched cohort at baseline: mean age 52 ± 13 years (60% female); weight 116 ± 25 kg, body mass index (BMI) 41 ± 9kg/m2, estimated glomerular filtration rate (eGFR); 70.4 ± 20 mL/min/1.73 m2, and median albumin-creatinine ratio (uACR) 2.0 mg/mmol (interquartile range (IQR): 0.9-5.2 mg/mmol). Bariatric surgery was associated with a 54% reduction in developing CKD compared to their matched non-bariatric cohort (adjusted hazard ratio [aHR]: 0.46; 95%CI: 0.24-0.85, P = 0.02). Among patients with microalbuminuria at baseline, bariatric surgery was protective against CKD (aHR: 0.42, 95%CI: 0.18-0.99, P = 0.050). eGFR was significantly increased from baseline favouring the bariatric group during 75% of the follow-up time (calculated mean difference between groups: 4.1 mL/min/1.73 m2; P < 0.05), especially at 5-year point (74.2 vs 67.8 mL/min/1.73 m2; P < 0.001). However, no significant change was observed with non-fatal CVD episodes (aHR: 0.36, 95%CI: 0.11-1.13, P = 0.079). Albumin levels were significantly reduced throughout the 2 years following the surgery (3.9 vs 4.1 g/dL, P < 0.001). uACR and total protein levels had little or no statistical association to the intervention.
Bariatric surgery may protect patients with diabetes with or without microalbuminuria against the risk of CKD and with a modest protective effect on non-fatal CVD risk. Bariatric surgery is also associated with improvements in overall renal outcomes such as eGFR.
The preventive and therapeutic effects of α-lipoic acid on ethylene glycol-induced calcium oxalate deposition in rats.
To investigate the effect of α-lipoic acid (α-LA) in the prevention and treatment of ethylene glycol-induced calcium oxalate deposition in a rat model and preliminary exploration of the mechanism.Sixty male Wistar rats were divided randomly and equally into six groups including two α-LA prevention groups, two α-LA therapeutic groups, one controlled group and one intervention group. Besides controlled group, other group received 1% glycol solution and 2 ml 2% ammonium chloride for 4 weeks as a stone inducer. The prevention groups received 0.1 and 0.2 mg/kg body weight/day/rat α-LA as food supplement during inducing stone and therapeutic groups received 0.1 and 0.2 mg/kg body weight/day/rat α-LA for 4 weeks after 4 weeks stone inducing.The volume of urine, the pH and magnesium levels in the preventive and therapeutic groups were higher in a dose-independent manner (p < 0.05), and urinary calcium was lower (p < 0.05). Antioxidant stress enzyme activity (glutathione, superoxide dismutase, catalase) in serum and kidney homogenates in the preventive and therapeutic groups underwent significant regeneration (p < 0.05) and malondialdehyde levels and the production of free radical moieties decreased. Pathological observation demonstrated that there was deformation due to renal tubular expansion in the control group, greater visible inflammatory cell infiltration into the interstitial spaces and partial destruction of the glomerular structures. α-lipoic acid improved the lesions to varying degrees. The extent of crystal deposition was lower in the preventive and therapeutic groups compared with the control group (p < 0.05).The present study indicated that α-LA provides both preventive and therapeutic effects against the deposition of calcium oxalate crystals in rats.
Untargeted Contrast-Enhanced Ultrasound Versus Contrast-Enhanced Computed Tomography: A Differential Diagnostic Performance (DDP) Study for Kidney Lesions.
Histopathology is the ‘gold standard’ for diagnosing renal cell carcinoma but is limited by sample size. Contrast-enhanced ultrasound can differentiate malignant and benign lesions, but the Chinese guidelines on the management of renal cell carcinoma do not include this method. The purpose of this study was to compare the diagnostic parameters of contrast-enhanced ultrasound against those of contrast-enhanced computed tomography for detecting kidney lesions, with histopathology considered the reference standard.Patients with suspected kidney lesions from prior grayscale ultrasonography and computed tomography were included in the analysis (n=191). The contrast-enhanced ultrasound, contrast-enhanced computed tomography, and histopathology data were collected and analyzed. A solid, enhanced mass was considered a malignant lesion, and an unenhanced mass or cyst was considered a benign lesion. The Bosniak criteria were used to characterize the lesions.Contrast-enhanced ultrasound and contrast-enhanced computed tomography both detected that 151 patients had malignant tumors and 40 patients had benign tumors. No significant differences in the tumors and their subtypes were reported between contrast-enhanced ultrasound and histopathology (p=0.804). Chromophobe renal cell carcinoma was detected through contrast-enhanced computed tomography (n=1), but no such finding was reported by contrast-enhanced ultrasound. A total of 35 cases of papillary renal cell carcinoma were reported through contrast-enhanced ultrasound while 32 were reported through histopathology.Contrast-enhanced ultrasound might be safe and as accurate as histopathology in diagnosing kidney lesions, especially renal cell carcinoma. Additionally, this study provides additional information over histopathology and has an excellent safety profile.III.
Aquaporin locus (12q13.12) might contribute to susceptibility of temporomandibular joint disorder associated with periodontitis.
Aquaporins (AQPs) are membrane channels that provide for transport of water and other small molecules across the lipid bilayer of cells. Their function is essential for physiologic processes such as cell volume regulation, chondrocyte hypertrophy during appendicular skeletal growth, water reabsorption in the kidney tubules, and water excretion by the salivary glands. The ten AQP isoforms show tissue specificity and are involved in different pathologies and inflammatory diseases. This study addresses the hypothesis that arthritis, periodontitis, and temporomandibular joint disorders (TMDs) can be influenced by variation in the AQP genes at 12q13.12 locus. Salivary samples of 688 individuals were obtained from the Dental Registry and DNA Repository project at the University of Pittsburgh. Ten polymorphisms in four AQP genes (AQP1, 2, 5, and 6) were genotyped and correlated to disease status as reported by patients. Associations were found between the single nucleotide polymorphism (SNP) rs467323 in AQP2 and TMD in both genotypic (p = 0.03) and recessive (p = 0.02) models, and between rs1996315 in AQP6 and periodontitis (p = 0.05). Combined analysis of TMD and periodontitis showed an association with rs3741559 in AQP2 (p = 0.02). When conducting haplotype analysis of rs467323 and rs10875989 in AQP2, the haplotype CT showed an association with the TMD phenotype (p = 0.007). Our results suggest that the aquaporin locus at 12q13.12 may contribute to the pathogenesis of inflammatory conditions such as periodontitis and TMD. Thus, oral and skeletal health are correlated and potential susceptibility screening strategies may be developed.
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Omeprazole use and risk of chronic kidney disease evolution.
In recent years, the use of proton pump inhibitors (PPI), especially omeprazole, has been associated with development of chronic kidney disease (CKD). These drugs are widely used worldwide. Although some studies have found an association between the use of PPI and the onset of acute renal failure and CKD. This study aims to analyze the association between the continuous use of omeprazole and the progression of CKD in adult and elderly individuals.A retrospective cohort study was conducted with patients followed up at a nephrology clinic in Brazil, in 2016 and 2017.