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Diabetes mellitus represents a group of metabolic diseases characterized by hyperglycemia from defects in insulin secretion, action, or both. The prevalence of type 2 diabetes mellitus, characterized by insulin resistance, has increased over time in the UK, and is the most prevalent cause of chronic kidney disease (CKD). Cardiovascular complications are a major cause of mortality for these patients. Stanniocalcin (STC), originally identified in bony fish as a hormone regulating calcium levels, has since been found in mammals, including humans. In fish, STC functions as an antihypercalcemic factor. Mammals possess 2 STC orthologues, STC-1 and STC-2, with STC-1 demonstrating significant sequence and functional conservation across species. Unlike fish, STC-1 is not normally present in the blood of healthy humans. However, it can be detected in certain conditions such as pregnancy, cancer, and CKD. In humans, STC-1 has diverse roles, including modulation of calcium and phosphate homeostasis, and it is implicated in kidney and cardiovascular protection. It has been reported that STC-1 has antioxidant, anti-inflammatory, and antiapoptotic activities, playing a role in renoprotection in diabetic nephropathy. This review explores the molecular biology of STC-1, its physiological functions, and its emerging role in GKDs, particularly diabetic and cardiovascular diseases. We highlight its potential protective mechanisms against hypercalcemia, its antioxidant and anti-inflammatory properties, and its cardioprotective properties in ischemia-reperfusion. Further research into STC-1 could provide new insights into therapeutic strategies for managing diseases characterized by calcium imbalance and lead to new treatments for the cardiovascular morbidity associated with diabetic kidney disease., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency., Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l). Patients were assigned 1:1 to intravenous (IV) iron therapy, or placebo. An 8-week exercise program commenced at week 4. The primary outcome was the mean between-group difference in 6-minute walk test (6MWT) at 4 weeks. Secondary outcomes included 6MWT at 12 weeks, transferrin saturation (TSAT), serum ferritin (SF), Hb, renal function, muscle strength, functional capacity, quality of life, and adverse events at baseline, 4 weeks, and at 12 weeks. Mean between-group differences were analyzed using analysis of covariance models., Results: Among 75 randomized patients, mean (SD) age for iron therapy ( n  = 37) versus placebo ( n  = 38) was 54 (16) versus 61 (12) years; estimated glomerular filtration rate (eGFR) (34 [12] vs. 35 [11] ml/min per 1.73 m 2 ], TSAT (23 [12] vs. 21 [6])%; SF (57 [64] vs. 62 [33]) μg/l; Hb (122.4 [9.2] vs. 127 [13.2] g/l); 6MWT (384 [95] vs. 469 [142] meters) at baseline, respectively. No significant mean between-group difference was observed in 6MWT distance at 4 weeks. There were significant increases in SF and TSAT at 4 and 12 weeks ( P  < 0.02), and Hb at 12 weeks ( P  = 0.009). There were no between-group differences in other secondary outcomes and no adverse events attributable to iron therapy., Conclusion: This trial did not demonstrate beneficial effects of IV iron therapy on exercise capacity at 4 weeks. A larger study is needed to confirm if IV iron is beneficial in nondialysis patients with CKD who are iron-deficient., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Diabetic kidney disease (DKD) accounts for >40% cases of chronic kidney disease (CKD) globally. Hypertension is a major risk factor for progression of DKD and the high incidence of cardiovascular disease and mortality in these people. Meticulous management of hypertension is therefore crucial to slow down the progression of DKD and reduce cardiovascular risk. Randomized controlled trial evidence differs in type 1 and type 2 diabetes and in different stages of DKD in terms of target blood pressure (BP). Renin-angiotensin blocking agents reduce progression of DKD and cardiovascular events in both type 1 and type 2 diabetes, albeit differently according to the stage of CKD. There is emerging evidence for the benefit of sodium glucose cotransporter 2, nonsteroidal selective mineralocorticoid antagonists, and endothelin-A receptor antagonists in slowing progression and reducing cardiovascular events in DKD. This UK guideline, developed jointly by diabetologists and nephrologists, has reviewed all available current evidence regarding the management of hypertension in DKD to produce a set of comprehensive individualized recommendations for BP control and the use of antihypertensive agents according to age, type of diabetes, and stage of CKD (https://ukkidney.org/sites/renal.org/files/Management-of-hypertension-and-RAAS-blockade-in-adults-with-DKD.pdf). A succinct summary of the guideline, including an infographic, is presented here., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: There is paucity of literature comparing outcomes of kidney transplant patients with COVID-19 to that of dialysis and waitlisted patients. This report describes our data, provides comparative analysis, together with a meta-analysis of published studies, and describes our protocols to restart the transplant program., Methods: Data were analyzed on kidney transplant, dialysis, and waitlisted patients tested positive for SARS-CoV-2 (nasopharyngeal swab polymerase chain reaction [PCR] test) between March 1, 2020, and June 30, 2020, together with a meta-analysis of 16 studies., Results: Twenty-three of 1494 kidney transplant patients tested positive for SARS-CoV-2 compared with 123 of 1278 hemodialysis patients (1.5% vs. 9.6%, P < 0.001) and 12 of 253 waitlisted patients (1.5% vs. 4.7%, P = 0.002). Nineteen patients required hospital admission, of whom 6 died and 13 developed AKI. The overall case fatality ratio was 26.1% compared with patients on hemodialysis (27.6%, P = 0.99) and waitlisted patients (8.3%, P = 0.38). Within our entire cohort, 0.4% of transplant patients died compared with 0.4% of waitlisted patients and 2.7% of hemodialysis patients. Patients who died were older (alive [median age 71 years] vs. dead [median age 59 years], P = 0.01).In a meta-analysis of 16 studies, including ours, the pooled case fatality ratio was 24% (95% confidence interval [CI] 19%, 28%); AKI proportion in 10 studies was 50% (95% CI 45%, 56%), with some evidence against no heterogeneity between studies ( P = 0.02)., Conclusions: From our cohort of transplant patients, a significantly lower proportion of patients contracted COVID-19 compared with waitlisted and dialysis patients. The case fatality ratio was comparable to that of the dialysis cohort and to a pooled case fatality ratio from a meta-analysis of 16 studies. The pooled AKI ratio in the meta-analysis was similar to our results., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)