Nephrology最新文献

Aim: This study aimed to describe the epidemiology of kidney replacement therapy (KRT) in Aotearoa New Zealand and assess the impact of residential location on access to kidney transplantation.

Methods: AcceSS and Equity in Transplantation (ASSET), a health-linked data platform, was used to identify people commencing KRT in New Zealand from 2006 to 2019 and analyse regional epidemiology. Health services were classified as 'transplanting', 'intermediate' or 'remote' depending on their degree of separation from a transplant centre. Multiple logistic regression modelling was used to assess the predictors of deceased donor waitlisting or living donor transplantation within 6 months after starting KRT. Web-based mapping software was used to develop interactive geospatial maps.

Results: The cohort was 7704 people newly starting KRT. Living in an intermediate [odds ratio (OR): 0.73 (95% confidence interval (CI): 0.61-0.88)] or remote [OR: 0.38 (95% CI: 0.27-0.54)) region and Māori (OR: 0.35 (95% CI: 0.28-0.44)], Pacific [OR: 0.32 (95% CI: 0.24-0.42)) and Asian (OR: 0.66 (95% CI: 0.50-0.87)] ethnicity were associated with a decreased likelihood of timely waitlisting or transplantation. Regional maps can be explored here.

Conclusion: There is marked geospatial and ethnic variation in the epidemiology of kidney failure and access to kidney transplantation across New Zealand. Geospatial mapping of kidney failure epidemiology and transplantation outcomes can provide opportunities to direct resources towards populations at greatest need.

Background: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD) is the predominant isoform of the catalytic subunit of PI3K in lymphocytes. Based on comprehensive bioinformatics, this study explores the functions of PIK3CD in diabetic kidney disease (DKD) progression in mice and B lymphocyte activity.

Methods: Non-obese diabetic (NOD) mice that spontaneously develop DKD were applied as animal models. Lentiviral vector-mediated PIK3CD silencing was introduced in mice, followed by histological staining and biomarker assessments to evaluate DKD-associated symptoms. The activity of the Akt/mTOR signalling pathway was determined by western blot analysis. Following bioinformatics analyses, the interaction between POU class 2 homeobox 2 (POU2F2) and PIK3CD in B lymphocytes was determined by chromatin immunoprecipitation and luciferase reporter assays. Their functions in B cell function were identified by MTT, flow cytometry and IgG deposition assessment.

Results: PIK3CD was found to be highly expressed in the kidney of DKD mice. Knockdown of PIK3CD inactivated the Akt/mTOR signalling, thus ameliorating tissue injury and fibrosis, enhancing the expression of AQP1 and decreasing urinary NGAL contents, UACR, BUN and β-NAG/creatinine ratio. These effects were negated by the Akt-specific activator SC79. POU2F2 was found to promote PIK3CD transcription by binding to its promoter, thus activating the Akt/mTOR pathway. Knockdown of POU2F2 suppressed B cell proliferation in vitro and decreased B cell population and IgG deposition in the mouse kidney. However, these trends were reversed upon additional PIK3CD overexpression.

Conclusion: This study demonstrates that POU2F2 mediates PIK3CD-dependent Akt/mTOR signalling activation, thus enhancing B lymphocyte function and promoting DKD progression.

Aim: Editors-in-Chief (EiC) play a key role as gatekeepers in academic medicine, often shaping research agendas. Women have historically been underrepresented in editorial leadership roles in academic medicine. The purpose of this study was to examine gender representation among EiC of contemporary transplantation and nephrology journals.

Methods: This cross-sectional study evaluated gender disparities among EiC of transplantation and nephrology medical journals. The study population was drawn from journals in two subject categories (1) 'Transplantation' and (2) 'Urology and Nephrology' in the 2023 Journal Citation Reports. Binary gender classification (woman/man) was determined by the names/pronouns used to describe the EiC on the journal or institutional webpage. The primary outcome was the proportion of women EiC. Secondary outcome was the proportion of women EiC based on journal topic, location and metrics. Descriptive statistics were used. Gender differences were compared using students t-test or Fisher's exact test.

Results: A total of 79 EiC were identified of which 16 (20%) were women and 63 (80%) were men (p < .001). Transplantation and nephrology journals had 21% and 20% women EiC, respectively. The proportion of women to men EiC was not impacted by journal category (p = .93), journal location (p = .61), journal impact factor (p = .71) or quartile (p = .59).

Conclusion: There was a disparity in gender representation in EiC in nephrology and transplantation journals, with men holding 80% of all positions. These findings, among growing evidence of gender disparity, highlight a need for targeted efforts to promote gender equity in academic medicine.

End-stage renal disease (ESRD) patients frequently encounter challenges at the time of dialysis catheter insertion from concomitantly associated with thoracic central venous obstruction (TCVO). TCVO complicates the placement of tunnelled dialysis catheters (TDCs). In cases where TCVO is unexpectedly encountered and TDC insertion becomes difficult, central venoplasty followed by catheter reinsertion is required. This report details a novel technique to salvage a TDC that was trapped at the TCVO site after removal of the peel-away sheath. We describe the case of a 67-year-old diabetic male ESRD patient on haemodialysis since 2017, with history of multiple prior accesses, who presented with acute thrombosis of his arteriovenous fistula. TDC placement was attempted via the left internal jugular vein (IJV). Angiography revealed severe stenosis at the left brachiocephalic vein-superior vena cava confluence, necessitating venoplasty. Post-venoplasty, the TDC could not be advanced past the IJV venous entry site due to unfavourable catheter tip profile. Utilising a double guidewire railroad technique, the TDC was successfully reinserted, ensuring functional dialysis. The technique carries potential risks, which mandates careful hemodynamic monitoring and prophylactic measures. In conclusion, percutaneous placement of a TDC following a central venoplasty is at times life-saving in patients with exhausted peripheral vascular access and concomitant TCVO. In the absence of a peel-away sheath, TDC reinsertion using a double guidewire railroad technique is a helpful technique for salvaging the catheter, especially in financially-constrained settings.

Exploration of the incidence and outcomes of Acute Kidney Injury (AKI) broadly, and sepsis associated AKI specifically, in Aboriginal and Torres Strait Islander (First Nations) people has been limited. We compared a nested cohort of First Nations people drawn from a multinational randomised controlled trial of hydrocortisone in septic shock, to a cohort matched for age, sex and severity of illness. Acute Kidney Injury was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, as well as incident use of kidney replacement therapy (KRT). Major Adverse Kidney Events (MAKE) were described as the composite of death, new dialysis requirement or persisting kidney dysfunction at hospital discharge. A cohort of 57 Aboriginal and/or Torres Strait Islander patients with septic shock was identified. 91.2% (52) of the First Nations cohort met KDIGO criteria for Stage 1 AKI or greater and 63% (36) met Stage 3 criteria. 59.6% (34) of the First Nations required dialysis as compared to 45.6% (26) in the matched cohort. 60.7% (34) of First Nations participants met criteria for MAKE at hospital discharge. The proportions requiring dialysis at 6, 12 and 24 months were 8.3%, 9.1% and 6.9% respectively. The incidences of AKI and MAKE reported in this First Nations cohort are substantially higher than in previously published cohorts of patients with sepsis, even those that use sensitive definitions of AKI. Measures to promote better management of infectious diseases in First Nations communities are required.

The incidence and prevalence of genetic diseases associated with chronic kidney disease (CKD) have been increasing over the last decades. To identify the monogenic causes of kidney stone disorders linked to CKD, a comprehensive literature review was conducted to identify monogenic genes causing nephrolithiasis and CKD. Among 41 identifiable monogenic causes of nephrolithiasis the following diseases primary hyperoxaluria familial hypomagnesemia with hypercalciuria and nephrocalcinosis, cystinuria; Dent disease, adenine phosphoribosyltransferase deficiency, Lesch-Nyhan syndrome, and idiopathic Infantile hypercalciuria have been linked to CKD and may progress to end-stage kidney disease (ESKD). Autosomal dominant hypocalcemia and Bartter syndrome (BS) are also hereditary kidney diseases that can cause urolithiasis but are rarely associated with CKD. A few BS type III can be complicated with CKD. A substantial number of kidney stone patients with genetic disorders progress to CKD. Genetic diagnosis should be initiated in all children presenting with kidney stones.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a syndrome commonly observed in subjects with impaired renal function. Phosphate metabolism has been implicated in the pathogenesis of CKD-MBD and according to the phosphorocentric hypothesis may be the key player in the pathogenesis of these abnormalities. As phosphorous is an essential component for life, absorption from the bowel, accumulation and release from the bones, and elimination through the kidneys are all homeostatic mechanisms that maintain phosphate balance through very sophisticated feedback mechanisms, which comprise as main actors: vitamin D (VD), parathyroid hormone (PTH), calciproteins particles (CPPs), fibroblast growth factor-23 (FGF-23) and other phosphatonins and klotho. Indeed, as the renal function declines, factors such as FGF-23 and PTH prevent phosphate accumulation and hyperphosphatemia. However, these factors per se may be responsible for the organ damages associated with CKD-MBD, such as bone osteodystrophy and vascular calcification. We herein review the current understanding of the CKD-MBD focusing on phosphorous metabolism and the impact of phosphate manipulation on surrogate and hard outcomes.

Aim: Inflammation plays a critical role in the progression of diabetic nephropathy. Peroxisome proliferator-activated receptor gamma (PPARγ) and its coactivator PPARγ coactivator-1 alpha (PGC-1α) enhance mitochondrial biogenesis and cellular energy metabolism but inhibit inflammation. However, the molecular mechanism through which these two proteins cooperate in the kidney remains unclear. The aim of the present study was to investigate this mechanism.

Methods: HK-2 human proximal tubular cells were stimulated by inflammatory factors, the expression of PPARγ and PGC-1α were determined via reverse transcription-quantitative polymerase chain reaction (PCR) and western blotting (WB), and DNA binding capacity was measured by an EMSA. Furthermore, db/db mice were used to establish a diabetic nephropathy model and were administered PPARγ and PGC-1α activators. Kidney injury was evaluated microscopically, and the inflammatory response was assessed via WB, immunohistochemistry and immunofluorescence staining. Besides, HK-2 cells were stimulated by high glucose and inflammatory factors with and without ZLN005 treatment, the expression of PPARγ, PGC-1α, p-p65 and p65 were determined via qPCR and WB.

Results: Our results revealed that both TNF-α and IL-1β significantly decreased PPARγ and PGC-1 expression in vitro. Cytokines obviously decreased PPARγ DNA binding capacity. Moreover, we detected rapid activation of the NF-κB pathway in the presence of TNF-α or IL-1β. PPARγ and PGC-1α activators effectively protected against diabetic nephropathy and suppressed NF-κB expression both in db/db mice and HK-2 cells.

Conclusion: PPARγ and its coactivator PGC-1α actively participate in protecting against renal inflammation by regulating the NF-κB pathway, which highlights their potential as therapeutic targets for renal diseases.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant neurocutaneous disease. Arterial hypertension is one of its uncommon complications, which is supposed to be caused by renal cysts or angiomyolipomas. Few studies have been reported in the literature on renal artery stenosis (RAS) as the cause of hypertension in TSC. Hence, we reported a boy who presented with uncontrolled hypertension under five anti-hypertension drugs and was diagnosed with TSC complicated with left RAS. His high blood pressure was relieved by percutaneous transluminal renal angioplasty (PTRA). In one and a half years follow-up, his blood pressure was normal whilst he took four anti-hypertensive drugs. In conclusion, children with TCS complicated with hypertension should be carefully screened for RAS, which might be relieved by percutaneous balloon dilatation.

Anti-phospholipid syndrome (APS) nephropathy is an autoimmune disease that is sometimes accompanied by systemic lupus erythematosus (SLE). Here, we report the use of rituximab to treat a case of APS nephropathy in a SLE patient with recurrent vascular thrombosis. A 52-year-old woman, who had been diagnosed with SLE 11 years earlier, was referred to a nephrology clinic for evaluation of azotaemia and proteinuria. She had experienced spontaneous abortion at 35 years of age. The patient had been diagnosed with right popliteal thrombosis at 39 years of age, and with left pulmonary artery thrombosis and SLE at 41 years of age. Before admission, she was undergoing anticoagulant and immunosuppressive therapies, with follow-up in the rheumatology clinic. At her last outpatient clinic visit before admission, she exhibited mild bilateral lower-limb pitting oedema, impaired renal function and proteinuria. Renal biopsy revealed arteriolar wall thickening, with thrombi in the capillary lumina and marked inflammatory cell infiltration in the interstitium. The patient was treated with warfarin and high-dose corticosteroids. Intravenous rituximab (500 mg) was also administered twice at a 4-week interval. Her renal function did not worsen any further, and her proteinuria decreased. Here we report the successful use of rituximab to treat APS nephropathy in a patient with SLE, who had progressive renal insufficiency.