Longitudinal Trajectories of Biomarkers of Kidney Tubular Function in Type 1 Diabetes.

Introduction: Tubular biomarkers may shed insight into progression of kidney tubulointerstitial pathology complementary to traditional measures of glomerular function and damage.

Methods: We examined trajectories of tubular biomarkers in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC Study) of type 1 diabetes (T1D). Biomarkers were measured in a subset of 220 participants across 7 time points over 26 years.

Associations of Kidney Tubular Biomarkers With Incident Macroalbuminuria and Sustained Low eGFR in DCCT/EDIC.

Objective: Tubulointerstitial injury contributes to diabetic kidney disease (DKD) progression. We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D).

Research Design And Methods: We performed a case-cohort study examining associations of tubular biomarkers, measured across seven time points spanning ∼30 years, with incident macroalbuminuria ("severely elevated albuminuria," urinary albumin excretion rate [AER] ≥300 mg/day) and sustained low estimated glomerular filtration rate (eGFR) (persistent eGFR <60 mL/min/1.

Surveillance Imaging Strategies for Pituitary Adenomas: When, How Frequent, and When to Stop.

Objective: To describe a practical approach of when and how often to perform imaging, and when to stop imaging pituitary adenomas (PAs).

Methods: A literature review was carried out and recommendations provided are derived largely from personal experience.

Results: Magnetic resonance imaging is the mainstay imaging modality of choice in the assessment, treatment planning, and follow-up of PAs.

Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement.

This Consensus Statement from an international, multidisciplinary workshop sponsored by the Pituitary Society offers evidence-based graded consensus recommendations and key summary points for clinical practice on the diagnosis and management of prolactinomas. Epidemiology and pathogenesis, clinical presentation of disordered pituitary hormone secretion, assessment of hyperprolactinaemia and biochemical evaluation, optimal use of imaging strategies and disease-related complications are addressed. In-depth discussions present the latest evidence on treatment of prolactinoma, including efficacy, adverse effects and options for withdrawal of dopamine agonist therapy, as well as indications for surgery, preoperative medical therapy and radiation therapy.

Effects of metformin and intensive lifestyle interventions on the incidence of kidney disease in adults in the DPP/DPPOS.

Aims: We analyzed the incidence of kidney disease in the Diabetes Prevention Program Outcomes Study (DPPOS) by originally randomized treatment group assignment: Intensive Lifestyle (ILS), Metformin (MET) or Placebo (PLB).

Methods: The current analyses used a time-to-event approach in which the primary outcome was kidney disease, ascertained as urine albumin-to-creatinine ratio (ACR) ≥ 3.39 mg/mmol (30 mg/g) or eGFR <45 mL/min/1.

MPOWERED Trial Open-Label Extension: Long-term Efficacy and Safety Data for Oral Octreotide Capsules in Acromegaly.

Context: The MPOWERED core trial (NCT02685709) and open-label extension (OLE) phase investigated long-term efficacy and safety of oral octreotide capsules (OOC) in patients with acromegaly. Core trial primary endpoint data demonstrated noninferiority to injectable somatostatin receptor ligands (iSRLs). Core trial completers were invited to participate in the OLE phase.

Relationships Between the Cumulative Incidences of Long-term Complications in Type 1 Diabetes: The DCCT/EDIC Study.

Objective: To describe the relationships between the cumulative incidences of long-term complications in individuals with type 1 diabetes (T1D) and assess whether observed associations are independent of age, duration of diabetes, and glycemic levels.

Methods: Proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), reduced estimated glomerular filtration rate (eGFR), amputations, cardiovascular disease (CVD), and mortality were assessed in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study over ∼30 years.

Research Design And Results: The cumulative incidence of complications ranged from 3% (amputations) to 37% (CSME).

Urinary Angiotensinogen in Patients With Type 1 Diabetes With Microalbuminuria: Gender Differences and Effect of Intensive Insulin Therapy.

Introduction: Angiotensinogen (AOG) is the precursor of peptides of the renin angiotensin system (RAS). Because insulin up-regulates transcriptional factors that normally repress kidney AOG synthesis, we evaluated urinary AOG (uAOG) in patients with type 1 diabetes (T1D) and microalbuminuria who are receiving either intensive or conventional insulin therapy.

Methods: Urine samples from participants of the Diabetes Control and Complications Trial (DCCT) were used for the following: (i) uAOG/creatinine measurements in 103 patients with microalbuminuria and 103 patients with normoalbuminuria, matched for age, gender, disease duration, and allocation to insulin therapy; and (ii) uAOG/creatinine measurements from patients with microalbuminuria allocated to intensive insulin therapy ( = 58) or conventional insulin therapy ( = 41) after 3 years on each modality.

Optimal Frequency of Urinary Albumin Screening in Type 1 Diabetes.

Objective: Kidney disease screening recommendations include annual urine testing for albuminuria after 5 years' duration of type 1 diabetes. We aimed to determine a simple, risk factor-based screening schedule that optimizes early detection and testing frequency.

Research Design And Methods: Urinary albumin excretion measurements from 1,343 participants in the Diabetes Control and Complications Trial and its long-term follow-up were used to create piecewise-exponential incidence models assuming 6-month constant hazards.

Durable biochemical response and safety with oral octreotide capsules in acromegaly.

Objective: The objective of this study is to report results from the open-label extension (OLE) of the OPTIMAL trial of oral octreotide capsules (OOC) in adults with acromegaly, evaluating the long-term durability of therapeutic response.

Design: The study design is an OLE of a double-blind placebo-controlled (DPC) trial.

Methods: Patients completing the 36-week DPC period on the study drug (OOC or placebo) or meeting predefined withdrawal criteria were eligible for OLE enrollment at 60 mg/day OOC dose, with the option to titrate to 40 or 80 mg/day.

Glucocorticoid receptor blockers.

Mifepristone is the only glucocorticoid receptor antagonist currently approved for the treatment of Cushing's syndrome. Although originally developed as an abortifacient due to its blockade of the progesterone receptor, a number of case reports documented its efficacy as a glucocorticoid receptor blocker going back to 1985. The SEISMIC trial, published in 2012, provided sufficient data on efficacy and adverse effects for regulatory approval.

KDOQI US Commentary on the KDIGO 2020 Clinical Practice Guideline for Diabetes Management in CKD.

In October 2020, KDIGO (Kidney Disease: Improving Global Outcomes) published its first clinical practice guideline directed specifically to the care of patients with diabetes and chronic kidney disease (CKD). This commentary presents the views of the KDOQI (Kidney Disease Outcomes Quality Initiative) work group for diabetes in CKD, convened by the National Kidney Foundation to provide an independent expert perspective on the new guideline. The KDOQI work group believes that the KDIGO guideline takes a major step forward in clarifying glycemic targets and use of specific antihyperglycemic agents in diabetes and CKD.

Early Trajectory of Estimated Glomerular Filtration Rate and Long-term Advanced Kidney and Cardiovascular Complications in Type 1 Diabetes.

Objective: Rapid loss of estimated glomerular filtration rate (eGFR) within its normal range has been proposed as a strong predictor of future kidney disease. We investigated this association of eGFR slope early in the course of type 1 diabetes with long-term incidence of kidney and cardiovascular complications.

Research Design And Methods: The annual percentage change in eGFR (slope) was calculated during the Diabetes Control and Complications Trial (DCCT) for each of 1,441 participants over a mean of 6.

Maintenance of response to oral octreotide compared with injectable somatostatin receptor ligands in patients with acromegaly: a phase 3, multicentre, randomised controlled trial.

Background: Despite biochemically responding to injectable somatostatin receptor ligands (iSRLs), many patients with acromegaly experience treatment burdens. We aimed to assess maintenance of biochemical response and symptomatic control with oral octreotide capsules versus iSRLs in patients with acromegaly who previously tolerated and responded to both.

Methods: This global, open-label, randomised controlled phase 3 trial was done in 29 clinical sites in Austria, France, Germany, Hungary, Italy, Lithuania, Russia, Serbia, Spain, and the USA.

Consensus on diagnosis and management of Cushing's disease: a guideline update.

Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants.

Management of Diabetes Mellitus in Patients With CKD: Core Curriculum 2022.

The most common cause of kidney failure in the United States and across the world is diabetes mellitus (DM). Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in persons with diabetes, and chronic kidney disease (CKD) further increases overall CVD risk. It is important to individualize glycemic targets for patients to maintain glucose levels that will reduce the development and progression of complications while avoiding hypoglycemia.

Oral octreotide capsules for the treatment of acromegaly: comparison of 2 phase 3 trial results.

Purpose: Results are presented from 2 to 3 trials investigating oral octreotide capsules (OOC) as an alternative to injectable somatostatin receptor ligands (iSRLs) in the treatment of acromegaly.

Methods: CH-ACM-01 was an open-label trial (N = 155) and CHIASMA OPTIMAL was a double-blind placebo-controlled (DPC) trial (N = 56), both investigating OOC as maintenance therapy for patients with acromegaly who were biochemical responders receiving iSRLs.

Results: Baseline characteristics in both trials reflected those expected of patients with acromegaly responding to treatment and were similar between trials, despite differences in inclusion criteria.

Prolactin and Other Pituitary Disorders in Kidney Disease.

Prolactin levels are increased in chronic kidney disease (CKD) as a result of reduced clearance and increased secretion. Hyperprolactinemia manifests as galactorrhea and hypogonadism. Treatment of hyperprolactinemia should focus on improving bothersome galactorrhea or hypogonadism by using dopamine agonists and/or replacement of sex hormone(s).