Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021.

People with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been shown to be beneficial in people with diabetes in slowing progression of kidney disease and reducing cardiovascular events. However, randomised controlled trial evidence differs in type 1 and type 2 diabetes and different stages of CKD in terms of target blood pressure. Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mechanism for the development and progression of CKD and cardiovascular disease. Randomised trials demonstrate that RAAS blockade is effective in preventing/ slowing progression of CKD and reducing cardiovascular events in people with type 1 and type 2 diabetes, albeit differently according to the stage of CKD. Emerging therapy with sodium glucose cotransporter-2 (SGLT-2) inhibitors, non-steroidal selective mineralocorticoid antagonists and endothelin-A receptor antagonists have been shown in randomised trials to lower blood pressure and further reduce the risk of progression of CKD and cardiovascular disease in people with type 2 diabetes. This guideline reviews the current evidence and makes recommendations about blood pressure control and the use of RAAS-blocking agents in different stages of CKD in people with both type 1 and type 2 diabetes.

Use of a GH receptor antagonist (GHRA) to explore the relationship between GH and IGF-I in adults with severe GH deficiency (GHD).

OBJECTIVE: At diagnosis, approximately 50% of adults with severe GH deficiency (GHD) have an IGF-I within the reference range. It is unclear whether in such patients serum IGF-I levels are regulated by factors other than GH. DESIGN AND PATIENTS: We performed a double-blind, randomized, placebo-controlled, cross-over study to investigate the effect of the GH receptor antagonist - pegvisomant (20 mg daily for 14 days) on GH and IGF-I levels in three cohorts: patients with GHD and a normal IGF-I (NORMS); patients with GHD and a low IGF-I (LOWS) and healthy volunteers (CONS). RESULTS: Pegvisomant decreased IGF-I in CONS and NORMS [158.5 (101-206) vs. 103 (77-125) microg/l, P < 0.01; 124 (81-136) vs. 95 (51-113) microg/l, P < 0.01 respectively], but not in LOWS [31 (< 31-32) vs. 34.5 (< 31-38) microg/l], and this was associated with an increase in mean 24 h GH in CONS [0.49 (0.12-0.89) to 1.38 (0.22-2.45) microg/l (P = 0.03)] and in NORMS [69 (0-320)% from 0.1 (< 0.1-0.13) to 0.17 (0.11-0.42) microg/l (P = 0.03)], but not in the LOWS. The peak GH response to arginine was increased by pegvisomant in CONS and NORMS [6.1 (0.8-9) vs. 20.4 (13.1-28.8) microg/l, P = 0.03; 0.4 (0.1-0.5) vs. 0.5 (0.3-0.6) microg/l, respectively], but not in LOWS. CONCLUSIONS: These data indicate that patients with severe GHD with a normal IGF-I are able to increase GH secretion in response to a pegvisomant-induced fall in IGF-I, whereas those with low IGF-I levels are unable to increase GH secretion. Therefore circulating IGF-I appears to be GH-independent in GHD patients with a low IGF-I, but remains partially GH-dependent in GHD patients with a normal IGF-I.

Variation in GH and IGF-I assays limits the applicability of international consensus criteria to local practice.

BACKGROUND: There is increasing reliance on consensus criteria for decision making. Recent criteria state that acromegaly is excluded by a nadir GH during an oral glucose tolerance test (OGTT) of < 1 microg/l and a normal level of IGF-I. OBJECTIVE: To study GH and IGF-I assay performance close to cut-off values for active acromegaly. DESIGN AND METHODS: Two serum samples known to give borderline results were sent to all centres participating in the UK National External Quality Assessment Service (NEQAS). Sample A was assigned to be a nadir during an OGTT and sent for GH assessment to 104 centres. Sample B, with a clinical scenario, was sent to 23 centres that measure IGF-I, and these centres were asked to measure IGF-I, interpret the result and provide the source of their reference ranges (RRs). RESULTS: For sample A, the median GH was 2.6 mU/l (range 1.04-3.5 mU/l). Applying a conversion factor (CF) of 2.0 (1 microg/l = 2 mU/l), the most negatively biased method classified 10% of the values consistent with acromegaly, while the most positively biased method classified all values as consistent with the diagnosis. Applying a CF of 3.0 (1 microg/l = 3 mU/l), only 11% of results were consistent with acromegaly. For sample B, the median IGF-I was 50.8 nmol/l (range 24.3-60.9 nmol/l). All centres used age-related RRs. There was a 50% variation in the upper limit of the RRs between centres. Overall, 30% of the IGF-I results were against the diagnosis. There was little agreement in the RRs quoted by centres using the same method. CONCLUSION: Variability in assay performance, coupled with use of inappropriate CFs and RRs, undermines the applicability of international consensus criteria to local practice.