Lois A. Katz

Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial

BACKGROUND Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes. METHODS ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA(1c) concentrations (>7.5%), and cardiovascular disease (or >or=2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A(1c) [HbA(1c)] of <6.0%) or standard (7.0-7.9%) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291.7 micromol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620. FINDINGS 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1.00, 95% CI 0.88-1.14; p=1.00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0.96, 0.89-1.02; p=0.19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0.95, 95% CI 0.85-1.07, p=0.42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0.95, 0.89-1.01, p=0.12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive therapy (p<0.05). INTERPRETATION Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia. FUNDING US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.

Acquired cystic disease of kidney in chronic dialysis patients

Eight cases of acquired cystic disease of the kidney (ACDK) associated with chronic renal failure and hemodialysis are described. No patient had a family history or clinical evidence of congenital adult polycystic kidney disease (CAPKD). Glomerulonephritis was the cause of renal failure in 6, and pyelonephritis in 2. Massive renal and perirenal hemorrhage necessitated 3 nephrectomies in 2 patients. Single kidney weights did not exceed 280 Gm., a major feature in the distinction of ACDK from CAPKD. Morphologically, in addition to the usual stigmata of end-stage kidneys, 40 to 80 per cent of the renal parenchyma was replaced by small cysts. Continuity of cysts with tubules was established by nephron dissection.

Amyloidosis in Subcutaneous Heroin Abusers (' 'Skin Poppers' Amyloidosis' ')

Systemic amyloidosis has recently emerged as a major cause of nephropathy among heroin abusers in New York City. Although focal glomerulosclerosis is typically seen in intravenous drug abusers who present with the nephrotic syndrome, those who escape this complication are at risk for the later development of amyloidosis related to their use of the subcutaneous route. Twenty such addicts identified between 1981 and 1984 are described. Patients typically present with chronic suppurative skin infections, edema, the nephrotic syndrome, benign urinary sediment, and normal-sized or enlarged kidneys. Tubular dysfunction, particularly renal tubular acidosis and diabetes insipidus, is frequent. Progression of renal insufficiency is characteristically rapid. Prolonged survival of heroin abusers and exhaustion of intravenous access requiring recourse to the subcutaneous route underlie the occurrence of amyloidosis in the addict population. Chronic suppurative skin infection consequent to repeated subcutaneous injection appears to be the underlying cause.

Combined intensive blood pressure and glycemic control does not produce an additive benefit on microvascular outcomes in type 2 diabetic patients

A reduction of either blood pressure or glycemia decreases some microvascular complications of type 2 diabetes, and we studied here their combined effects. In total, 4733 older adults with established type 2 diabetes and hypertension were randomly assigned to intensive (systolic blood pressure less than 120 mm Hg) or standard (systolic blood pressure less than 140 mm Hg) blood pressure control, and separately to intensive (HbA1c less than 0.060) or standard (HbA1c 0.070-0.079) glycemic control. Prespecified microvascular outcomes were a composite of renal failure and retinopathy and nine single outcomes. Proportional hazard regression models were used without correction for type I error due to multiple tests. During a mean follow-up of 4.7 years, the primary outcome occurred in 11.4% of intensive and 10.9% of standard blood pressure patients (hazard ratio 1.08), and in 11.1% of intensive and 11.2% of standard glycemia control patients. Intensive blood pressure control only reduced the incidence of microalbuminuria (hazard ratio 0.84), and intensive glycemic control reduced the incidence of macroalbuminuria and a few other microvascular outcomes. There was no interaction between blood pressure and glycemic control, and neither treatment prevented renal failure. Thus, in older patients with established type 2 diabetes and hypertension, intensive blood pressure control improved only 1 of 10 prespecified microvascular outcomes. None of the outcomes were significantly reduced by simultaneous intensive treatment of glycemia and blood pressure, signifying the lack of an additional beneficial effect from combined treatment.

Effects of Intensive BP Control in CKD

The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n=1330) or <140 mm Hg (standard group; n=1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD (P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (-0.47 versus -0.32 ml/min per 1.73 m2 per year; P<0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.

The Role of Patients’ Explanatory Models and Daily-Lived Experience in Hypertension Self-Management

ABSTRACTBACKGROUNDUncontrolled hypertension remains a significant problem for many patients. Few interventions to improve patients’ hypertension self-management have had lasting effects. Previous work has focused largely on patients’ beliefs as predictors of behavior, but little is understood about beliefs as they are embedded in patients’ social contexts.OBJECTIVEThis study aims to explore how patients’ “explanatory models” of hypertension (understandings of the causes, mechanisms or pathophysiology, course of illness, symptoms and effects of treatment) and social context relate to their reported daily hypertension self-management behaviors.DESIGNSemi-structured qualitative interviews with a diverse group of patients at two large urban Veterans Administration Medical centers.PARTICIPANTS (OR PATIENTS OR SUBJECTS)African-American, white and Latino Veterans Affairs (VA) primary care patients with uncontrolled blood pressure.APPROACHWe conducted thematic analysis using tools of grounded theory to identify key themes surrounding patients’ explanatory models, social context and hypertension management behaviors.RESULTSPatients’ perceptions of the cause and course of hypertension, experiences of hypertension symptoms, and beliefs about the effectiveness of treatment were related to different hypertension self-management behaviors. Moreover, patients’ daily-lived experiences, such as an isolated lifestyle, serious competing health problems, a lack of habits and routines, barriers to exercise and prioritizing lifestyle choices, also interfered with optimal hypertension self-management.CONCLUSIONSDesigning interventions to improve patients’ hypertension self-management requires consideration of patients’ explanatory models and their daily-lived experience. We propose a new conceptual model — the dynamic model of hypertension self-management behavior — which incorporates these key elements of patients’ experiences.

Glomerular Sclerosis in Adults with Nephrotic Syndrome

Abstract Ten adults with the nephrotic syndrome and sterile pyuria are described. On biopsy they had varying degrees of glomerular sclerosis without proliferation. Interstitial inflammation and fib...

Olfaction and Hemodialysis: Baseline and Acute Treatment Decrements

The effect of hemodialysis (HD) on olfactory recognition and memory function was investigated in people receiving chronic HD treatment. Fifteen subjects were given an olfactory recognition task 0.5 h before and 0.5 h after a dialysis session in counterbalanced order. Ten dialysis patients received a verbal recall task twice. Ten age-matched normal subjects received the olfactory task twice. Results were: (1) olfactory scores in the HD group were significantly lower than control subjects scores; (2) within the dialysis sample, olfactory identification scores were significantly lower after treatment than before, and (3) there were no parallel decreases in memory performance of the dialysis group after a HD treatment. We therefore conclude that those subjects receiving HD treatment demonstrate acute and chronic deficits in olfactory recognition which are unlikely to be due to fatigue, cognitive disequilibrium, anticoagulant treatment or high levels of uremic toxins.

Functional Aortic Insufficiency — A Feature of Renal Failure

PRESENCE of an aortic diastolic murmur generally signifies organic valvular disease. Functional aortic insufficiency is unusual; its occasional occurrence has been attributed to such hemodynamic st...

Hemodialysis Using Femoral Vessel Cannulation

600 acute hemodialyses have been performed by a simplified method of percutaneous femoral vessel can nulation utilizing special equipment. Because skin incision was not required, repeated cannulation