The Gut-Kidney Axis: Putative Interconnections Between Gastrointestinal and Renal Disorders

Diabetic kidney disease (DKD) is a devastating condition associated with increased morbidity and premature mortality. The etiology of DKD is still largely unknown. However, the risk of DKD development and progression is most likely modulated by a combination of genetic and environmental factors. Patients with autoimmune diseases, like type 1 diabetes, inflammatory bowel disease, and celiac disease, share some genetic background. Furthermore, gastrointestinal disorders are associated with an increased risk of kidney disease, although the true mechanisms have still to be elucidated. Therefore, the principal aim of this review is to evaluate the impact of disturbances in the gastrointestinal tract on the development of renal disorders

The Gut-Kidney Axis : Putative Interconnections Between Gastrointestinal and Renal Disorders

Diabetic kidney disease (DKD) is a devastating condition associated with increased morbidity and premature mortality. The etiology of DKD is still largely unknown. However, the risk of DKD development and progression is most likely modulated by a combination of genetic and environmental factors. Patients with autoimmune diseases, like type 1 diabetes, inflammatory bowel disease, and celiac disease, share some genetic background. Furthermore, gastrointestinal disorders are associated with an increased risk of kidney disease, although the true mechanisms have still to be elucidated. Therefore, the principal aim of this review is to evaluate the impact of disturbances in the gastrointestinal tract on the development of renal disorders.Peer reviewe

Genetic basis of diabetic kidney disease and other diabetic complications

Diabetic kidney disease and other long-term complications are common in diabetes, and comprise the main cause of co-morbidity and premature mortality in individuals with diabetes. While familial clustering and heritability have been reported for all diabetic complications, the genetic background and the molecular mechanisms remain poorly understood. In recent years, genome-wide association studies have identified a few susceptibility loci for the renal complications as well as for diabetic retinopathy, diabetic cardiovascular disease and mortality. As for many complex diseases, the genetic factors increase the risk of complications in concert with the environment, and certain associations seem specific for particular conditions, for example, SP3-CDCA7 associated with end-stage renal disease only in women, or MGMT and variants on chromosome 5q13 associated with cardiovascular mortality only under tight glycaemic control. The characterization of the phenotypes is one of the main challenges for genetic research on diabetic complications, in addition to an urgent need to increase the number of individuals with diabetes with high quality phenotypic data to be included in future genetic studies.Peer reviewe

Genetic and epigenetic background of diabetic kidney disease

Diabetic kidney disease (DKD) is a severe diabetic complication that affects up to half of the individuals with diabetes. Elevated blood glucose levels are a key underlying cause of DKD, but DKD is a complex multifactorial disease, which takes years to develop. Family studies have shown that inherited factors also contribute to the risk of the disease. During the last decade, genome-wide association studies (GWASs) have emerged as a powerful tool to identify genetic risk factors for DKD. In recent years, the GWASs have acquired larger number of participants, leading to increased statistical power to detect more genetic risk factors. In addition, whole-exome and whole-genome sequencing studies are emerging, aiming to identify rare genetic risk factors for DKD, as well as epigenome-wide association studies, investigating DNA methylation in relation to DKD. This article aims to review the identified genetic and epigenetic risk factors for DKD

The nephrological perspective on SGLT-2 inhibitors in type 1 diabetes

Prevalence of type 1 diabetes mellitus (T1DM) is globally continuously increasing. T1DM is accompanied by a high risk of developing cardiovascular and renal comorbidities and is one of the leading causes of end-stage renal disease (ESRD). However, current therapeutic approaches for chronic and/or diabetic kidney disease (CKD/DKD) existed for a long time, and offer room for improvement, particularly in T1DM. In 2019, the European Medicines Agency (EMA) approved a first sodium/glucose co-transporter 2 inhibitor (SGLT-2i) and a first dual SGLT-1/-2i to improve glycaemic control, as an adjunctive treatment to insulin in persons with T1DM and a body mass index >27 kg/m(2). Of note, SGLT-1/2is and SGLT-2is are not approved by the Food and Drug Administration (FDA) as an adjunct treatment in T1DM, nor approved for the treatment of CKD or DKD by EMA and FDA. SGLT is have shown to mediate different renoprotective effects in type 2 diabetes mellitus in corresponding cardiovascular and renal outcome trials. First efficacy trials offer insights into potential positive effects on renal function and kidney disease of SGLTis in T1DM. This review summarizes and discusses latest available data on SGLT inhibition and provides an update on the nephrological perspective on SGLTis, specifically in T1DM. (c) 2020 Published by Elsevier B.V.Peer reviewe

Incidence rate patterns, cumulative incidence, and time trends for moderate and severe albuminuria in individuals diagnosed with type 1 diabetes aged 0-14 years : a population-based retrospective cohort study

Background The incidence and temporal trends of moderate and severe albuminuria during recent decades are poorly described in type 1 diabetes. We aimed to assess diabetes duration-specific incidence rates, cumulative incidence, and secular trends of albuminuria in type 1 diabetes in Finland. Methods We conducted a population-based, retrospective cohort study of a stratified random sample (n=1500) of all individuals diagnosed with type 1 diabetes before age 15 years during 1970-99 in Finland. The sampling frame was the database of the Finnish Institute for Health and Welfare. Individuals with an atypical clinical course, presentation of non-diabetic kidney disease, insufficient albumin excretion rate measurements, or unavailable medical records were excluded (final sample n=1430). Study participants were followed up until death, the event of interest (moderate or severe albuminuria or kidney failure), or the most recent event-free date. Medical records retrieved up to Dec 31, 2020 were systematically reviewed for albuminuria determinations. Moderate and severe albuminuria were categorised on the basis of international reference limits (two of three consecutive urine samples). Kidney failure was defined as dialysis treatment or kidney transplant. Cohorts defined by calendar year of diabetes diagnosis (1970-79, 1980-89, and 1990-99) were assessed. Patterns of duration-specific incidences were evaluated by fitting generalised additive models to the data, which were split into multiple observations of half-year duration. Cumulative incidences were calculated with Kaplan-Meier analysis. In analyses with kidney failure as the endpoint, competing risk for mortality was incorporated. Findings In our stratified random sample, 462 individuals were diagnosed with diabetes in 1970-79, 481 were diagnosed in 1980-89, and 487 were diagnosed in 1990-99. The incidence rate pattern of severe albuminuria changed over time; a peak at 15-19 years since diabetes onset in the 1970-79 cohort was not replicated in those diagnosed later. In the combined 1980-99 diagnosis-year cohorts, the incidence rate rose during the first 14 years after diabetes onset, after which it levelled off to a plateau. Between the 1970-79 and 1980-89 diabetes diagnosis cohorts, the cumulative incidence of severe albuminuria had approximately halved (hazard ratio [HR] 0.55 [95% CI 0.42-0.72] with the 1970-79 cohort as reference, p Interpretation Our analyses show that the cumulative incidence of severe albuminuria has decreased between 1970-79 and 1980-99; however, whether this decrease solely denotes a delay in albuminuria, or also a true prevention of albuminuria, needs to be investigated further. Nevertheless, diabetic kidney disease remains a significant complication of type 1 diabetes. Due to the robust association of diabetic kidney disease with premature mortality, novel therapies to improve prognosis are needed. Copyright (C) 2022 Elsevier Ltd. All rights reserved.Peer reviewe

Time trends in mortality in patients with type 1 diabetes: nationwide population based cohort study

Objective To examine short and long term time trends in mortality among patients with early onset (age 0-14 years) and late onset (15-29 years) type 1 diabetes and causes of deaths over time

Exercise and nutrition in type 1 diabetes : Insights from the FinnDiane cohort

Type 1 diabetes is a challenging disease, characterized by dynamic changes in the insulin need during life periods, seasons of the year, but also by everyday situations. In particular, changes in insulin need are evident before, during and after exercise and having meals. In the midst of different life demands, it can be very burdensome to achieve tight glycemic control to prevent late diabetes complications, and at the same time, to avoid hypoglycemia. Consequently, many individuals with type 1 diabetes are faced with diabetes distress, decreasing profoundly their quality of life. Today, the nationwide Finnish Diabetic Nephropathy (FinnDiane) Study, launched in 1997, has gathered data from more than 8,000 well-characterized individuals with type 1 diabetes, recruited from 93 centers all over Finland and has established its position as the world's leading project on studying complications in individuals with type 1 diabetes. Studying risk factors and mechanisms of diabetes complications is inconceivable without trying to understand the effects of exercise and nutrition on glycemic control and the development of diabetes complications. Therefore, in this paper we provide findings regarding food and exercise, accumulated during the 25 years of studying lives of Finnish people with type 1 diabetes.Peer reviewe

The Association of Severe Diabetic Retinopathy With Cardiovascular Outcomes in Long-standing Type 1 Diabetes : A Longitudinal Follow-up. Diabetes Care 2018;41:2487-2494 Response

Non peer reviewe