Nationwide survey of adolescents and young adults with end-stage kidney disease

Aim: To better understand the health‐care needs of adolescents and young adults (AYA) with end‐stage kidney disease (ESKD), we sought to describe the demographic characteristics of a national cohort. Methods: Data were retrieved from the Australia and New Zealand Dialysis and Transplant Registry. We included all patients aged 15–25 years, living in Australia and receiving renal replacement therapy (RRT) on 31 December 2009. Data included race, aetiology of kidney disease, postal code, transition and migration history. Results: A total of 495 AYA were receiving RRT in Australia giving a prevalence of 143 per million age‐related population. Sixty‐three per cent had a functioning transplant, 24% were receiving haemodialysis and 13% peritoneal dialysis. Median current age was 22 years (interquartile range (IQR) 19–24). The most prevalent cause of ESKD was glomerulonephritis (33%). The majority of patients lived in capital cities. Indigenous patients were more likely to live in more remote areas. Eighty‐five per cent of patients were currently receiving care at an adult unit and 35% of these patients had transitioned from a paediatric unit since starting RRT. The median number of patients per adult unit was 5 (IQR 3–10). Conclusions: The majority of Australian AYA with ESKD are managed in adult units; however, the number at any one unit is low. As most live in the capital cities there may be an opportunity to establish centralized services designed to cater for the needs of AYA patients. However, the needs of patients living in more remote areas, including a significant proportion of Indigenous patients, may not be met by such a model.     

Management of the Diabetic Patient with Advanced Chronic Kidney Disease

Diabetic kidney disease (DKD) is the leading cause of end‐stage renal disease (ESRD), and one of the most prevalent microvascular complications of both type 1 and type 2 diabetes. Additionally, risk of death is increased at all stages of DKD. As early as the microalbuminuric stage, the death rate approaches 20% per year. Therefore, management strategies should address reducing risk of mortality as well as progression to ESRD. DKD is associated with multiple co‐morbidities including hypertension, dyslipidemia, cardiovascular disease, anemia, and bone and mineral metabolism disorders (BMD). Anemia and BMD often occur earlier in the course of DKD than with other forms of chronic kidney disease. Pharmacological and dietary management of hyperglycemia, hypertension, dyslipidemia, anemia, and BMD pose specific challenges in DKD. However, with heightened awareness of risks and a multifactorial management approach, the impact of DKD on micro‐ and macrovascular complications and death can be reduced.     

加强对正常蛋白尿糖尿病肾脏疾病的认识

糖尿病肾脏疾病(DKD)是导致终末期肾脏病(ESRD)的主要原因,早期及时诊断对防治DKD进展非常重要。以往DKD临床诊断多注重尿白蛋白排泄率(UAER),并以此作为诊断与临床分期的重要依据。实际上许多糖尿病(DM)有时表现为无临床诊断价值的蛋白尿,而以肾功能减退为突出肾脏受累表现,即正常蛋白尿糖尿病肾脏疾病(NADKD),或称无蛋白尿糖尿病肾病(nonalbuminuric diabetic nephropathy),及糖尿病无蛋白尿肾功能不全(nonalbuminuric renal impairment in diabetes)。本文结合国内外研究现状,从流行病学、病理、临床特征、诊断及治疗等方面对NADKD进行了描述,以翼引起同行重视。     

Exercise and physical activity for people receiving peritoneal dialysis: Why not?

People with end‐stage kidney disease (ESKD) receiving peritoneal dialysis (PD) are physically inactive leading to low physical function and poor health outcomes. Guidelines recommend that nephrologists encourage PD patients to increase their activity levels; however, PD patients are often discouraged from participating in exercise programs because of perceived barriers and a lack of precision about the appropriate exercise regimen. This review suggests ways forward to assist nephrology professionals to encourage PD patients to exercise, instead of creating barriers. The paper draws on the literature in addition to the experience of programs in France, the United States, and Australia to demonstrate the possibilities when considering increasing physical activity in this group.     

微小RNA在糖尿病肾病发病机制中的研究进展

糖尿病肾病(diabetic kidney disease,DKD)是糖尿病(diabetes mellitus,DM)引起的微血管并发症之一,是DM患者预期寿命减少的主要原因。现已明确DKD发病机制与细胞外基质积累、氧化应激、炎症反应、自噬等有关。微小RNA(microRNA,miRNA)很稳定,可以在人的体液中检测到,作为肾脏疾病生物标志物获得了优势,并为肾脏疾病的诊断指标提供了补充。认识miRNA对DKD发病机制的调控作用,对DKD的诊治将有极大意义。本文对miRNA与DKD发病机制的相关性进行综述。     

Review: Metformin: Potential benefits and use in chronic kidney disease

Diabetes mellitus is the commonest cause of end‐stage renal failure in both Australia and New Zealand. In addition, the burden of diabetes is prominent in those with chronic kidney disease who have not yet reached the requirement for renal replacement therapy. While diabetes is associated with a higher incidence of mortality and morbidity in all populations studied with kidney disease, little is known about optimal treatment strategies for hyperglycaemia and the effects of glycaemic treatment in this large group of patients. Metformin is recommended as the drug of first choice in patients diagnosed with type 2 diabetes in the USA, Europe and Australia. There are potential survival benefits associated with the use of metformin in additional to recent studies suggesting benefits in respect to cardiovascular outcomes and metabolic parameters. The use of metformin has been limited in patients with renal disease because of the perceived risk of lactic acidosis; however, it is likely that use of this drug would be beneficial in many with chronic kidney disease. Thus the potential benefits and harms of metformin are outlined in this review with suggestions for its clinical use in those with kidney disease.     

Diabetic kidney disease in pediatric patients: A current review

In the last decades, a significant increase in the incidence of diabetic kidney disease (DKD) was observed concomitant with rising diabetes mellitus (DM) incidence. Kidney disease associated with DM in children and adolescents is represented by persistent albuminuria, arterial hypertension, progressive decline in estimated glomerular filtration rate to end-stage renal disease and increased cardiovascular and all-cause morbidity and mortality of these conditions. In medical practice, the common and still the “gold standard” marker for prediction and detection of diabetic kidney involvement in pediatric diabetes is represented by microalbuminuria screening even if it has low specificity to detect early stages of DKD. There are some known limitations in albuminuria value as a predictor biomarker for DKD, as not all diabetic children with microalbuminuria or macroalbuminuria will develop end-stage renal disease. As tubular damage occurs before the glomerular injury, tubular biomarkers are superior to the glomerular ones. Therefore, they may serve for early detection of DKD in both type 1 DM and type 2 DM. Conventional and new biomarkers to identify diabetic children and adolescents at risk of renal complications at an early stage as well as renoprotective strategies are necessary to delay the progression of kidney disease to end-stage kidney disease. New biomarkers and therapeutic strategies are discussed as timely diagnosis and therapy are critical in the pediatric diabetic population.     

Increases in renal replacement therapy in Australia and New Zealand: understanding trends in diabetic nephropathy

Aim: The incidence of end‐stage kidney disease (ESKD) has been increasing worldwide, with increasing numbers of older people, people with diabetic nephropathy and indigenous people. We investigated the incidence of renal replacement therapy (RRT) in Australia and New Zealand (NZ) to better understand the causes of these effects. Methods: Data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA)registry and relevant population data were used to investigate the incidence of RRT in five demographic groups: Indigenous and non‐indigenous Australians, Māori, Pacific Islanders and other New Zealanders, as well as differences between genders and age groups. Results: The numbers of patients commencing RRT each year increased by 321% between 1990 and 2009. This increase was largely driven by increases in patients with diabetic nephropathy. In 2009 35% of new patients had ESKD resulting from diabetic nephropathy 92% of which were type 2. Indigenous Australians, and Māori and Pacific people of NZ have elevated risks of commencing RRT due to diabetic nephropathy, although the risks compared with non‐indigenous Australians have decreased over time. A small element of lead time bias also contributed to this increase. Males are more likely to commence RRT due to diabetes than females, except among Australian Aborigines, where females are more at risk. There is a marked increase in older, more comorbid patients. Conclusions: Patterns of incident renal replacement therapy strongly reflect the prevalence of diabetes within these groups. In addition, other factors such as reduced risk of dying before reaching ESKD, and increased acceptance of older and sicker patients are also contributing to increases in incidence of RRT.     

High prevalence of colon adenomas in end‐stage kidney disease patients on hemodialysis undergoing renal transplant evaluation

The aim of this study was to determine whether patients with end‐stage kidney disease (ESKD) on hemodialysis (HD) undergoing kidney transplant evaluation are at higher risk for colonic neoplasia than the general population. This is a retrospective cohort study of patients with ESKD who underwent a first screening colonoscopy while undergoing kidney transplant evaluation. Data were collected on the prevalence of adenomatous polyps and advanced adenomas in 70 patients with ESKD and 70 controls, undergoing their first screening colonoscopy, matched for age, gender, and endoscopist. At the time of the colonoscopy, an average time on HD was 3.2 ± 2.9 yr. The prevalence of adenomatous polyps was significantly higher in ESKD on HD (54.3% vs. 32.9%, p = 0.008) than in controls. In a multivariate analysis controlling for other factors, ESKD on HD remained a risk factor for the presence of adenomas (OR 3.06, 95% CI 1.21, 7.73). No colonoscopy‐related complications were reported in the patients with ESKD on HD. We demonstrate a significantly higher prevalence of adenomatous polyps in patients with ESKD undergoing a first screening colonoscopy as part of kidney transplant evaluation. In addition, colonoscopy can be safely performed in this population.     

Interaction between socioeconomic deprivation and likelihood of pre‐emptive transplantation: influence of competing risks and referral characteristics – a retrospective study

Socioeconomic deprivation (SED) influences likelihood of pre‐emptive kidney transplantation (PET), but the mechanisms behind this are unclear. We explored the relationships between SED and patient characteristics at referral, which might explain this discrepancy. A retrospective cohort study was performed. SED was measured by Scottish Index of Multiple Deprivation (SIMD). Logistic regression evaluated predictors of PET. A competing risks survival analysis evaluated the interaction between SED and progression to end‐stage kidney disease (ESKD) and death. Of 7765 patients with follow‐up of 5.69 ± 6.52 years, 1298 developed ESKD requiring RRT; 113 received PET, 64 of which were from live donors. Patients receiving PET were “less deprived” with higher SIMD (5 ± 7 vs. 4 ± 5; P = 0.003). This appeared independent of overall comorbidity burden. SED was associated with a higher risk of death but not ESKD. Higher SIMD decile was associated with a higher likelihood of PET (OR 1.14, 95% CI 1.06, 1.23); the presence of diabetes and malignancy also reduced PET. SED was associated with reduced likelihood of PET after adjustment for baseline comorbidity, and this was not explained by risk of death or faster progression to ESKD. Education and outreach into transplantation should be augmented in areas with higher deprivation.     

糖尿病肾脏疾病的发病机制研究进展

糖尿病肾脏疾病(diabetic kidney disease,DKD)是影响全世界的公共卫生问题,是糖尿病患者发病和死亡的主要原因,也是终末期肾病的主要原因。因其缺乏有效的治疗手段,对其机制的研究一直是临床研究的热点。肾脏血流动力学变化、氧化应激、炎症等都与DKD的发病机制有关,而相关研究指出代谢记忆和表观遗传学对DKD的进展中起着重要的作用,在这篇综述中,将结合目前的最新研究概述DKD发病机制的进展。     

Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives

Diabetic kidney disease (DKD) is one of the major chronic complications of diabetes mellitus (DM), as well as a main cause of end-stage renal disease. Over the last few years, substantial research studies have revealed a contributory role of gut microbiota in the process of DM and DKD. Metabolites of gut microbiota like lipopolysaccharide, short-chain fatty acids, and trimethylamine N-oxide are key mediators of microbial–host crosstalk. However, the underlying mechanisms of how gut microbiota influences the onset and progression of DKD are relatively unknown. Besides, strategies to remodel the composition of gut microbiota or to reduce the metabolites of microbiota have been found recently, representing a new potential remedial target for DKD. In this mini-review, we will address the possible contribution of the gut microbiota in the pathogenesis of DKD and its role as a therapeutic target.     

Renin-angiotensin system blockers-SGLT2 inhibitors-mineralocorticoid receptor antagonists in diabetic kidney disease: A tale of the past two decades!

Several pharmacological agents to prevent the progression of diabetic kidney disease (DKD) have been tested in patients with type 2 diabetes mellitus (T2DM) in the past two decades. With the exception of renin-angiotensin system blockers that have shown a significant reduction in the progression of DKD in 2001, no other pharmacological agent tested in the past two decades have shown any clinically meaningful result. Recently, the sodium-glucose cotransporter-2 inhibitor (SGLT-2i), canagliflozin, has shown a significant reduction in the composite of hard renal and cardiovascular (CV) endpoints including progression of end-stage kidney disease in patients with DKD with T2DM at the top of renin-angiotensin system blocker use. Another SGLT-2i, dapagliflozin, has also shown a significant reduction in the composite of renal and CV endpoints including death in patients with chronic kidney disease (CKD), regardless of T2DM status. Similar positive findings on renal outcomes were recently reported as a top-line result of the empagliflozin trial in patients with CKD regardless of T2DM. However, the full results of this trial have not yet been published. While the use of older steroidal mineralocorticoid receptor antagonists (MRAs) such as spironolactone in DKD is associated with a significant reduction in albuminuria outcomes, a novel non-steroidal MRA finerenone has additionally shown a significant reduction in the composite of hard renal and CV endpoints in patients with DKD and T2DM, with reasonably acceptable side effects.     

Lifetime risk of end‐stage kidney disease in living donors for paediatric kidney transplant recipients in Australia and New Zealand – a retrospective study

Living kidney donors (LKD) for paediatric kidney transplant recipients (KTR) have a heightened motivation to donate for emotional reasons and the clear health benefits to the KTR. We hypothesized that the cohort of LKD for paediatric KTR (LKD‐P) includes motivated young parents with a higher lifetime end‐stage kidney disease (ESKD) risk compared to adult KTR (LKD‐A). Data from the Australia and New Zealand Dialysis and Transplant LKD Registry (2004–2015) was analysed to compare baseline characteristics and predonation ESKD risk in LKD‐P (n = 315) versus LKD‐A (n = 3448). LKD‐P were younger (median age 42 vs. 50 years; P < 0.001) and had a marginally higher lifetime ESKD risk (median 0.44% vs. 0.40%; P < 0.01), with a similar proportion of LKD exceeding 1% risk threshold (5.4% vs. 5.6%; P = NS). Compared to grandparents as LKD‐P, parents (median age 41 vs. 59 years; P < 0.001) had a higher lifetime ESKD (0.44% vs. 0.25%; P < 0.001). Although unique benefits to paediatric KTR justify the minor increase in lifetime ESKD risk in young parents, carefully selected grandparents are an alternative LKD‐P option, allowing parents to donate for subsequent transplants.     

Renal genetics in Australia: Kidney medicine in the genomic age

There have been few new therapies for patients with chronic kidney disease in the last decade. However, the management of patients affected by genetic kidney disease is rapidly evolving. Inherited or genetic kidney disease affects around 10% of adults with end‐stage kidney disease and up to 70% of children with early onset kidney disease. Advances in next‐generation sequencing have enabled rapid and cost‐effective sequencing of large amounts of DNA. Next‐generation sequencing‐based diagnostic tests now enable identification of a monogenic cause in around 20% of patients with early‐onset chronic kidney disease. A definitive diagnosis through genomic testing may negate the need for prolonged diagnostic investigations and surveillance, facilitate reproductive planning and provide accurate counselling for at‐risk relatives. Genomics has allowed the better understanding of disease pathogenesis, providing prognostic information and facilitating development of targeted treatments for patients with inherited or genetic kidney disease. Although genomic testing is becoming more readily available, there are many challenges to implementation in clinical practice. Multidisciplinary renal genetics clinics serve as a model of how some of these challenges may be overcome. Such clinics are already well established in most parts of Australia, with more to follow in future. With the rapid pace of new technology and gene discovery, collaboration between expert clinicians, laboratory and research scientists is of increasing importance to maximize benefits to patients and health‐care systems.     

糖尿病肾病规范化诊断研究进展

糖尿病肾脏疾病(DKD)是糖尿病的严重并发症,也是引起终末期肾病(ESRD)的常见原因。DKD的临床诊断通常有赖于糖尿病病史、尿白蛋白特点、有无视网膜病变及有无活动性尿沉渣等指标进行综合判断。但越来越多的研究提示了目前此临床诊断方法的高误诊率,本文就DKD的诊断进展进行了综述。     

Addressing the epidemic of chronic kidney disease in Australia

SUMMARY:   The Australia Diabetes, Obesity and Lifestyle Study (AUSDIAB) study provided, for the first time in Australia, a snapshot of the prevalence of kidney damage, reduced kidney function, hypertension and diabetes in the adult population. With this information, and the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) registry, that has recorded kidney failure statistics for many years, the extent of the chronic kidney disease burden in Australia is being better defined. This burden is even more pronounced in the Indigenous population where the incidence of kidney disease and kidney failure is increased several-fold.
Diabetes is the second most common cause of kidney failure among Australians. The number of patients with diabetes accepted to dialysis has doubled in the last 7 years, the mean body weight of patients commencing dialysis has increased 7 kg in the past decade and the mean age at acceptance to dialysis is rising in a linear fashion (presently 60 years). These facts, together with a static transplant rate, all point to the prevalence of dialysis likely staying at or increasing beyond the present yearly growth rate of 6–7%.
The evidence shows that a large proportion of chronic kidney disease patients are dying of cardiovascular risk factors before they reach dialysis or transplantation. There are many gaps in delivering appropriate preventative treatment to these patients. A relatively small reduction in the rise in dialysis numbers that might flow from an effective prevention of progression program, could make a significant impact on the spiralling numbers and associated cost of kidney failure treatment in Australia. We now need to develop and implement a national kidney disease strategy designed to address the whole continuum of chronic kidney disease from its earliest stage right through to dialysis and transplantation.     

Development and internal validation of machine learning algorithms for end-stage renal disease risk prediction model of people with type 2 diabetes mellitus and diabetic kidney disease

AimsDiabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) and is associated with increased morbidity and mortality in patients with diabetes. Identification of risk factors involved in the progression of DKD to ESRD is expected to result in early detection and appropriate intervention and improve prognosis. Therefore, this study aimed to establish a risk prediction model for ESRD resulting from DKD in patients with type 2 diabetes mellitus (T2DM).MethodsBetween January 2008 and July 2019, a total of 390 Chinese patients with T2DM and DKD confirmed by percutaneous renal biopsy were enrolled and followed up for at least 1 year. Four machine learning algorithms (gradient boosting machine, support vector machine, logistic regression, and random forest (RF)) were used to identify the critical clinical and pathological features and to build a risk prediction model for ESRD.ResultsThere were 158 renal outcome events (ESRD) (40.51%) during the 3-year median follow up. The RF algorithm showed the best performance at predicting progression to ESRD, showing the highest AUC (0.90) and ACC (82.65%). The RF algorithm identified five major factors: Cystatin-C, serum albumin (sAlb), hemoglobin (Hb), 24-hour urine urinary total protein, and estimated glomerular filtration rate. A nomogram according to the aforementioned five predictive factors was constructed to predict the incidence of ESRD.ConclusionMachine learning algorithms can efficiently predict the incident ESRD in DKD participants. Compared with the previous models, the importance of sAlb and Hb were highlighted in the current model.

Highlights

• What is already known? Identification of risk factors for the progression of DKD to ESRD is expected to improve the prognosis by early detection and appropriate intervention.
• What this study has found? Machine learning algorithms were used to construct a risk prediction model of ESRD in patients with T2DM and DKD. The major predictive factors were found to be CysC, sAlb, Hb, eGFR, and UTP.
• What are the implications of the study? In contrast with the treatment of participants with early-phase T2DM with or without mild kidney damage, major emphasis should be placed on indicators of kidney function, nutrition, anemia, and proteinuria for participants with T2DM and advanced DKD to delay ESRD, rather than age, sex, and control of hypertension and glycemia.

     

糖尿病肾脏疾病生物标记物的研究进展

糖尿病肾脏疾病(DKD)是糖尿病常见的并发症之一,也是终末期肾病的主要原因。由于治疗手段有限,DKD的早期诊断和病程预测对于改善临床管理尤为重要。尽管蛋白尿、血肌酐等被认为是DKD早期诊断、病程评估的重要指标,但实际上它们的诊断效能非常有限。因此,亟需寻找更具诊断或预测价值的DKD生物标记物。本文就近年来DKD生物标记物的研究新进展作一综述,为诊断策略的开发提供思路。     

An expanded nationwide view of chronic kidney disease in Aboriginal Australians

We summarize new knowledge that has accrued in recent years on chronic kidney disease (CKD) in Indigenous Australians. CKD refers to all stages of preterminal kidney disease, including end‐stage kidney failure (ESKF), whether or not a person receives renal replacement therapy (RRT). Recently recorded rates of ESKF, RRT, non‐dialysis CKD hospitalizations and CKD attributed deaths were, respectively, more than sixfold, eightfold, eightfold and threefold those of non‐Indigenous Australians, with age adjustment, although all except the RRT rates are still under‐enumerated. However, the nationwide average Indigenous incidence rate of RRT appears to have stabilized. The median age of Indigenous people with ESKF was about 30 years less than for non‐Indigenous people, and 84% of them received RTT, while only half of non‐Indigenous people with ESKF did so. The first‐ever (2012) nationwide health survey data showed elevated levels of CKD markers in Indigenous people at the community level. For all CKD parameters, rates among Indigenous people themselves were strikingly correlated with increasing remoteness of residence and socio‐economic disadvantage, and there was a female predominance in remote areas. The burden of renal disease in Australian Indigenous people is seriously understated by Global Burden of Disease Mortality methodology, because it employs underlying cause of death only, and because deaths of people on RRT are frequently attributed to non‐renal causes. These data give a much expanded view of CKD in Aboriginal people. Methodologic approaches must be remedied for a full appreciation of the burden, costs and outcomes of the disease, to direct appropriate policy development.