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.

Management of adults with diabetes on the haemodialysis unit: summary of guidance from the Joint British Diabetes Societies and the Renal Association.

Diabetic nephropathy remains the principal cause of end-stage renal failure in the UK and its prevalence is set to increase. People with diabetes and end-stage renal failure on maintenance haemodialysis are highly vulnerable, with complex comorbidities, and are at high risk of adverse cardiovascular outcomes, the leading cause of mortality in this population. The management of people with diabetes receiving maintenance haemodialysis is shared between diabetes and renal specialist teams and the primary care team, with input from additional healthcare professionals providing foot care, dietary support and other aspects of multidisciplinary care. In this setting, one specialty may assume that key aspects of care are being provided elsewhere, which can lead to important components of care being overlooked. People with diabetes and end-stage renal failure require improved delivery of care to overcome organizational difficulties and barriers to communication between healthcare teams. No comprehensive guidance on the management of this population has previously been produced. These national guidelines, the first in this area, bring together in one document the disparate needs of people with diabetes on maintenance haemodialysis. The guidelines are based on the best available evidence, or on expert opinion where there is no clear evidence to inform practice. We aim to provide clear advice to clinicians caring for this vulnerable population and to encourage and improve education for clinicians and people with diabetes to promote empowerment and self-management.

Foundation doctors working at night: what training opportunities exist?

INTRODUCTION: Foundation Training is designed for doctors in their first two years of post-graduation. The number of foundation doctors (FD) in the UK working nights has reduced because of a perception that clinical supervision at night is unsatisfactory and that minimal training opportunities exist. We aimed to assess the value of night shifts to FDs and hypothesised that removing FDs from nights may be detrimental to training. METHODS: Using a survey, we assessed the number of FDs working nights in London, FDs views on working nights and their supervision at night. We evaluated whether working at night, compared to daytime working provided opportunities to achieve foundation competencies. RESULTS: 83% (N = 2157/2593) of FDs completed the survey. Over 90% of FDs who worked nights felt that the experience they gained improved their ability to prioritise, make decisions and plan. FDs who worked nights reported higher scores for achieving competencies in history taking (2.67 vs. 2.51; p = 0.00), examination (2.72 vs. 2.59; p = 0.01) and resuscitation (2.27 vs. 1.96; p = 0.00). The majority (65%) felt adequately supervised. CONCLUSIONS: Our survey has demonstrated that FDs find working nights a valuable experience, providing important training opportunities, which are additional to those encountered during daytime working.

Renal cytokines improve early after bariatric surgery.

BACKGROUND: Bariatric surgery has been suggested to improve arterial hypertension and renal function. This prospective controlled observational study aimed to investigate changes in renal inflammation, renal function and arterial blood pressure before and after bariatric surgery. METHODS: Blood pressure was measured, and urine and blood samples were collected from 34 morbidly obese patients before and 4 weeks after bariatric surgery. Serum levels of cystatin C, creatinine, albumin, cholesterol and C-reactive protein (CRP) were measured, along with urinary cytokine/creatinine ratios for macrophage migration inhibitory factor (MIF), monocyte chemotactic protein (MCP) 1, chemokine ligand (CCL) 18 and CCL-15. RESULTS: Mean(s.e.m.) bodyweight dropped from 124·1(2·6) to 114·8(2·4) kg (P < 0·001) and mean arterial blood pressure decreased from 105·7(1·8) to 95·5(1·2) mmHg (P < 0·001) in 4 weeks. Systemic and urinary inflammatory markers improved, with a reduction in serum CRP level (P < 0·001), and decreased urinary MIF/creatinine (P < 0·001), MCP-1/creatinine (P < 0·001) and CCL-18/creatinine (P = 0·003) ratios. In contrast, urinary CCL-15/creatinine ratios did not change and the glomerular filtration rate, measured by serum cystatin C, was unchanged (P = 0·615). CONCLUSION: Surgically induced weight loss contributed to a decrease in blood pressure and markers of renal inflammation. The reduced levels of CRP and urinary cytokines suggest that bariatric surgery attenuates systemic and renal inflammatory status.

Determinants of near fatality in acute severe asthma.

PURPOSE: The data extrapolated from cases of acute severe asthma that narrowly miss being fatal may prove valuable in the identification of the factors implicated in mortality. The purpose of this study was, therefore, to identify determinants of near fatality in patients with acute severe asthma. PATIENTS AND METHODS: We studied 81 patients with acute severe asthma in whom mechanical ventilation was required. Near fatality was defined as the occurrence of respiratory arrest and/or coma necessitating emergency tracheal intubation and resuscitation. In the cases that were not regarded as near fatal, tracheal intubation was performed electively because of deteriorating arterial blood gas values and/or the anticipation of exhaustion. Various continuous and categorical variables were compared in these two groups of patients. Patients with a hyperacute attack (period from onset of attack to mechanical ventilation less than 3 hours) were specifically sought and studied to determine the impact of such a course on near fatality. RESULTS: The "attack duration" (period from onset of attack to mechanical ventilation) was an important determinant of near fatality and of the subsequent clinical course. It was shorter in the group with a near-fatal episode (p < 0.03), and hyperacute attacks were uniformly near fatal. The attack duration correlated positively with the duration of the requirement for mechanical ventilation (p < 0.01). A longer attack duration was associated with an increased likelihood of the occurrence of major atelectasis (p < 0.01). There was no evidence of a relationship between near fatality and the side effects of bronchodilators as regards hypokalemia, arrhythmias, or cardiotoxicity. There was evidence of considerable under-treatment in the patient population as a whole, particularly in regard to the use of corticosteroids. CONCLUSIONS: A short attack duration is associated with an increased risk of near fatality in acute severe asthma. This is particularly evident in hyperacute attacks. Hyperacute attacks resolve rapidly once bronchodilator therapy has been instituted, suggesting that smooth muscle spasm is the predominant pathogenetic mechanism. The importance of routine anti-inflammatory therapy in mild to moderate asthma requires re-emphasis but, in addition, all patients should be provided with, and educated in the use of, bronchodilator rescue therapy, which should be available at all times. Despite current trends, the use of regular, prophylactic bronchodilator therapy in strict conjunction with anti-inflammatory agents may still be indicated. There is little evidence in the present data obtained from near-fatal cases to support the concept that cardiotoxicity related to bronchodilators contributes significantly to mortality from asthma.

Requirements for the induction of allospecific CD8+ suppressor T cells in the rat primary mixed lymphocyte response. CD4+, CD45R+ T cells, or supernatant factor.

We examined the requirements for the induction of the MLR-generated allospecific CD8+ suppressor T cells in the rat. Depleting the responder population of CD4+ T cells before initiating the primary MLR abrogates the generation of day-5 CD8+ T suppressor effectors. Readdition of at least 10% CD4+ T cells to the CD4+ depleted primary MLR reconstitutes suppressor cell generation. Using the anti-CD45R monoclonal antibody OX22, we also show that the T suppressor inducer cells are CD4+ CD45R+. Using a dual chamber Transwell culture system, which allows cells to be co-incubated without direct cell-to-cell contact, we show that a soluble factor/s, produced during the course of the primary MLR, is capable of inducing naive CD8+ T cells to become suppressor effectors but only when these CD8 T cells are in direct contact with allogeneic stimulators. Allospecificity is conferred by the stimulator cells and not by the suppressor-inducer factor. The supernatant of day-5 primary MLR is also capable of inducing antigen-specific suppressor effectors from naive CD8+ T cells, and also only in the presence of allogeneic stimulator cells. Recombinant human IL-2, in doses that are up to five times the amount present in the supernatant cultures, is unable to induce suppressor-effector cells from naive CD8+ T cells. We conclude that, to become allospecific suppressor effectors, naive CD8+ T cells require contact with allogeneic stimulator cells and either CD4+ CD45R+ suppressor inducer cells or suppressor inducer factor/s produced during the course of the primary MLR.

Verrucous squamous cell carcinoma.

Verrucous squamous cell carcinoma involving the plantar aspect of the foot is a relatively rare and generally slow growing tumor that is capable of great local destruction. Diagnosis is based on history, clinical appearance and, most importantly, deep biopsy. A case report is presented, along with a literature review of the history, treatment and prognosis of this rare entity.

Type II essential mixed cryoglobulinaemia: presentation, treatment and outcome in 13 patients.

The long-term clinical course of patients with primary Type II essential mixed cryoglobulinaemia is unclear as many reports fail to separate this group from patients with Type III disease. We have reviewed 13 patients with Type II essential mixed cryoglobulinaemia who presented to the Hammersmith Hospital between 1976 and 1990. All patients had a cryoglobulin level greater than 0.1 mg/ml (range 0.27-6.50 mg/ml), and characterization of the cryoglobulin in all cases revealed the presence of a monoclonal IgM kappa component with rheumatoid factor activity together with polyclonal IgG. All patients had evidence of activation of the classical pathway of complement with greatly reduced levels of C4, while C3 levels were moderately reduced in three patients. All patients had skin disease and joint symptoms were reported by nine patients, with erosive arthritis in one. Eight patients had peripheral sensorimotor neuropathy. Renal disease was observed in 10 patients, manifesting as raised creatinine level, proteinuria or haematuria. Renal tissue was examined in eight patients: in six the appearances were those of a mesangiocapillary glomerulonephritis Type I while in the other two patients there was a mesangioproliferative glomerulonephritis, in one diffuse and in the other focal and segmental. Glomerular capillary 'hyaline thrombi' were found in six biopsies, extracapillary proliferation was found in three and evidence of vasculitis was found in all eight. Liver biopsy showed macronodular cirrhosis in one patient, while a second with recurrent episodes of jaundice showed only chronic inflammatory changes. No patient was positive for hepatitis B surface antigen; however one patient had low titre anti-hepatitis B surface antibody. Normochromic normocytic anaemia was present in nine patients. Bone marrow examination was carried out in 13 patients at presentation to our unit: 10 showed no evidence of a lymphoproliferative disorder, while three suggested the presence of a non-Hodgkin's lymphoma (some years after original presentation in all three). Unusual clinical features included one patient with retinal vasculitis and one patient with severe pulmonary haemorrhage.

Captopril-enhanced 99mTc DTPA scintigraphy in the detection of renal-artery stenosis.

The value of captopril-enhanced 99mTc DTPA scintigraphy as a screening test for renovascular disease was prospectively studied in 44 hypertensive patients suspected to have renal-artery stenosis. Renal impairment (plasma creatinine greater than 130 mumol/l) was present in 29 patients. At angiography 13 patients had unilateral stenosis, two bilateral stenosis, and 29 patients had no renovascular disease. Captopril induced a fall in split renal function in the kidney ipsilateral to the stenosis in all patients with unilateral disease (mean 52 +/- 23% to 44 +/- 21% of total renal function; P less than 0.001). A positive captopril scintigram (defined as a fall of 5% or more in split renal function) had a sensitivity of 85% and a specificity of 72% in the detection of unilateral renal-artery stenosis. Captopril-enhanced 99mTc DTPA scintigraphy is a promising non-invasive screening test for the detection of renal-artery stenosis.