Increased vulnerability to COVID-19 in chronic kidney disease.

BACKGROUND: The significance of chronic kidney disease on susceptibility to COVID-19 and subsequent outcomes remains unaddressed. OBJECTIVE: To investigate the association of estimated glomerular filtration rate (eGFR) on risk of contracting COVID-19 and subsequent adverse outcomes. METHODS: Rates of hospital-diagnosed COVID-19 were compared across strata of eGFR based on conditional logistic regression using a nested case-control framework with 1:4 matching of patients diagnosed with COVID-19 with controls from the Danish general population on age, gender, diabetes and hypertension. Risk of subsequent severe COVID-19 or death was assessed in a cohort study with comparisons across strata of eGFR based on adjusted Cox regression models with G-computation of results to determine 60-day risk standardized to the distribution of risk factors in the sample. RESULTS: Estimated glomerular filtration rate was inversely associated with rate of hospital-diagnosed COVID-19: eGFR 61-90 mL/min/1.73m2 HR 1.13 (95% CI 1.03-1.25), P = 0.011; eGFR 46-60 mL/min/1.73m2   HR 1.26 (95% CI 1.06-1.50), P = 0.008; eGFR 31-45 mL/min/1.73m2 HR 1.68 (95% CI 1.34-2.11), P < 0.001; and eGFR ≤ 30 mL/min/1.73m2 3.33 (95% CI 2.50-4.42), P < 0.001 (eGFR > 90 mL/min/1.73m2 as reference), and renal impairment was associated with progressive increase in standardized 60-day risk of death or severe COVID-19; eGFR > 90 mL/min/1.73m2 13.9% (95% CI 9.7-15.0); eGFR 90-61 mL/min/1.73m2 16.1% (95% CI 14.5-17.7); eGFR 46-60 mL/min/1.73m2 17.8% (95% CI 14.7-21.2); eGFR 31-45 mL/min/1.73m2 22.6% (95% CI 18.2-26.2); and eGFR ≤ 30 mL/min/1.73m2 23.6% (95% CI 18.1-29.1). CONCLUSIONS: Renal insufficiency was associated with progressive increase in both rate of hospital-diagnosed COVID-19 and subsequent risk of adverse outcomes. Results underscore a possible vulnerability associated with impaired renal function in relation to COVID-19.

Lymphopenia and neutropenia are associated with subsequent incident proteinuria in Danish patients with systemic lupus erythematosus.

Objective: The aim of this study was to investigate whether incident proteinuria in patients with systemic lupus erythematosus (SLE) was preceded by changes in blood lymphocytes and neutrophil counts and/or neutrophil-lymphocyte ratio (NLR).Method: SLE patients with no proteinuria before or at the time of classification were included. Longitudinal data on SLE manifestations, vital status, and SLE-associated medications were collected during clinical visits and chart review. Laboratory data were collected through a nationwide database. Lymphopenia, severe lymphopenia, and neutropenia were defined as values below 0.8 × 109, 0.5 × 109, and 2.0 × 109 cells/L, respectively. High NLR was defined as values above the median. Proteinuria was defined by at least two measurements of elevated urine protein excretion (> 0.5 g/day). Hazard ratios (HRs) were calculated by Cox modelling using time-dependent continuous and binary covariates based on multiple laboratory measurements adjusted for use of immunosuppressants.Results: In total, 260 SLE patients were available for the analysis, of whom 30 (12%) developed incident proteinuria following the diagnosis of SLE. Median follow-up time was 73.5 months. Lymphocyte and neutrophil counts, but not NLR, were associated with incident proteinuria. HRs for incident proteinuria were 2.71 for lymphopenia [95% confidence interval (CI) 1.20-6.11], 4.73 for severe lymphopenia (95% CI 1.93-11.59), and 2.54 for neutropenia (95% CI 1.14-5.65).Conclusion: Lymphopenia and neutropenia predicted the risk of first-time proteinuria independently of immunosuppressants.

Delirium detection using relative delta power based on 1-minute single-channel EEG: a multicentre study.

BACKGROUND: Delirium is frequently unrecognised. EEG shows slower frequencies (i.e. below 4 Hz) during delirium, which might be useful in improving delirium recognition. We studied the discriminative performance of a brief single-channel EEG recording for delirium detection in an independent cohort of patients. METHODS: In this prospective, multicentre study, postoperative patients aged ≥60 yr were included (n=159). Before operation and during the first 3 postoperative days, patients underwent a 5-min EEG recording, followed by a video-recorded standardised cognitive assessment. Two or, in case of disagreement, three delirium experts classified each postoperative day based on the video and chart review. Relative delta power (1-4 Hz) was based on 1-min artifact-free EEG. The diagnostic value of the relative delta power was evaluated by the area under the receiver operating characteristic curve (AUROC), using the expert classification as the gold standard. RESULTS: Experts classified 84 (23.3%) postoperative days as either delirium or possible delirium, and 276 (76.7%) non-delirium days. The AUROC of the relative EEG delta power was 0.75 [95% confidence interval (CI) 0.69-0.82]. Exploratory analysis showed that relative power from 1 to 6 Hz had significantly higher AUROC (0.78, 95% CI 0.72-0.84, P=0.014). CONCLUSIONS: Delirium/possible delirium can be detected in older postoperative patients based on a single-channel EEG recording that can be automatically analysed. This objective detection method with a continuous scale instead of a dichotomised outcome is a promising approach for routine detection of delirium. CLINICAL TRIAL REGISTRATION: NCT02404181.

Association Between Orthostatic Hypotension and Handgrip Strength With Successful Rehabilitation in Elderly Hip Fracture Patients.

OBJECTIVE: To investigate the relationship between orthostatic hypotension (OH) and muscle strength versus time to successful rehabilitation within elderly patients with hip fracture. DESIGN: A prospective, observational cohort study. Handgrip strength was measured at the day of admission and OH as soon as possible after surgery. Cox proportional hazard modeling was used to investigate the relationship between OH or handgrip strength (kg) and time to successful rehabilitation, expressed as hazard ratios (HRs). OH was defined as a decrease in systolic blood pressure of ≥20mmHg or diastolic blood pressure of ≥10mmHg after postural change (dichotomous). Handgrip strength was measured with a hand dynamometer (continuous). SETTING: General hospital. PARTICIPANTS: Patients (N=116) aged ≥70 years with a hip fracture were recruited on the day of hospital admission. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary outcome was time to successful rehabilitation, which was defined as discharge to patients' own homes. RESULTS: During a median follow-up period of 36 days (interquartile range, 9-57d), 103 patients (89%) were successfully rehabilitated. No statistically significant relationships were found between OH and time to successful rehabilitation (HR=1.05; 95% confidence interval [CI], .67-1.66). Also, handgrip strength and successful rehabilitation were not statistically significantly related (HR=1.03; 95% CI, .99-1.06). CONCLUSIONS: OH measured during the first days of hospitalization is not related to time to successful rehabilitation in patients with hip fracture who have undergone surgery. Although no significant relationship was seen in the present study, the width of the CIs does not exclude a relevant relationship between handgrip strength and time to successful rehabilitation.

[Circulatory failure : Out- and inpatient management]. / Kreislaufschwäche : Ambulantes und stationäres Management.

Circulatory insufficiency is often understood as symptomatic hypotension due to various causes. The clinical result of circulatory dysregulation is arterial hypotension. The manifestation of hypotension is often divided into chronic and acute forms. Chronic hypotension can be distinguished etiopathogenetically into primary and secondary hypotension. Acute hypotension is usually equated to circulatory shock. While patients with chronic hypotension should be seen primarily by their general practitioner, patients with acute hypotension and a frequently severe clinical manifestation should be evaluated in the emergency department or, if there is a specific cause, directly in the acute clinic. Standardization of diagnostic and therapeutic pathways in both out- and inpatient care-not only for the management of circulatory weakness-would be an improvement not only in regards to patient care, but also with respect to healthcare economics.

[Diagnostic image (356). A man with a painfully distended abdomen and a mass on the plain abdominal radiograph]. / Diagnose in beeld (356). Een man met een gezwollen, pijnlijke buik en een massa op de buikoverzichtsfoto.

A 44-year-old man had abdominal pain, abdominal swelling and constipation. A plain abdominal radiograph showed signs of an ileus and as an unrelated finding an extensively calcified former renal transplant.

Relationship between clinical outcomes and Dutch frailty score among elderly patients who underwent surgery for hip fracture.

BACKGROUND: Frailty is a geriatric condition that is associated with an increased risk of mortality and functional decline. To date, mainly the Groningen Frailty Indicator (GFI) and Hospital Safety Management (VeiligheidsManagementSysteem [VMS]) frailty score are used to determine frailty in several hospitals in the Netherlands. However, it is yet unknown, which method has the best predictive value on clinical outcomes. OBJECTIVE: The aim of this study was to investigate the predictive value of GFI and VMS on clinical outcomes among patients who underwent hip fracture surgery. DESIGN: This is a prospective observational cohort study. METHODS: We selected all patients aged 70 years or higher, who underwent hip fracture surgery in our general hospital, between November 2014 and November 2015. Among all patients, VMS, GFI and Barthel-20 index (BI) were assessed. McNemar's paired test and Cohen's κ were used to examine the difference and the level of agreement between the two scoring methods. Kaplan-Meier and multivariable regression analyses were performed to determine overall survival and mortality, respectively, 3 years and 30 days after surgery. RESULTS: A total of 280 patients were included in the study. The median follow-up was 25 months. No systematic difference was found between the two methods (P=0.237), while a fair level of agreement could be measured (κ=0.363 [95% CI =0.23-50]). VMS showed a statistically significant difference in overall survival as compared to nonfrail patients (57 vs 80%, respectively [P logrank <0.001] with an HR of 3.5 [95% CI =2.1-5.7; P<0.001]). Classification according to GFI yielded a lower but still significant HR 2.3 (95% CI =1.2-4.1; P=0.008). CONCLUSION: VMS can be used in classifying frailty, whereby VMS frailty score is associated with clinical outcomes as overall survival mortality in older patients with hip fracture and who underwent surgery.

This is an older men's world: A qualitative study of men's experiences with prostate cancer.

PURPOSE: Prostate cancer is highly prevalent and invasive among older men. Not knowing their experiences hampers care and support to men with prostate cancer and prostate cancer survivors. This study aims to provide insight into older men's experiences with prostate cancer in order to improve personalised care. METHODS: A qualitative research design through semi-structured interviews with 22 older men with prostate cancer was conducted in two areas of the Netherlands in 2015. Patients were selected through systematic non-probabilistic sampling. The transcripts were analysed with conventional content analysis and affinity diagramming. RESULTS: Four themes emerged from the data: impact of prostate cancer, dealing with prostate cancer and treatment, involvement of and with others, and experiences with professional care and the care trajectory. The way patients dealt with prostate cancer and their experiences with the care they received varied. Overall, hospital care was rated positively, and communication was a crucial determinant of the patient's satisfaction or dissatisfaction. Some patients lacked information about their health status, which may have influenced decision-making processes. Some were reluctant to talk about their disease with other people and sometimes hesitated to ask for help. CONCLUSION: Despite many positive care experiences, some patients felt that the communication, information provision and decision-making were inadequate. Vulnerable patients with severe complications or limited social support may need additional psychosocial care. Lowering the threshold for patients to ask for help and the availability of a professional with expert knowledge about prostate cancer and ageing may decrease unnecessary hardship and increase personal strengths.

Habitual dietary phosphorus intake and urinary excretion in chronic kidney disease patients: a 3-day observational study.

Hyperphosphatemia in chronic kidney disease (CKD) is associated with vascular calcification, cardiovascular morbidity and mortality. The aim of this study was to estimate the daily dietary phosphorus intake compared with recommendations in CKD patients and to evaluate the reproducibility of the 24-h urinary phosphorus excretion. Twenty CKD patients stage 3-4 from the outpatient clinic, collected 24-h urine and kept dietary records for 3 consecutive days. The mean daily phosphorus intake was 1367±499, 1642±815 and 1426±706 mg/day, respectively (P=0.57). The mean urinary phosphorus excretion was 914±465, 954±414 and 994±479 mg/day, respectively (P=0.21). In this population of CKD patients stage 3-4 the daily phosphorus intake was above the recommended. Twenty-four-hour urinary phosphorus excretion was reproducible and the data indicate that a single 24-h urine collection is sufficient to estimate the individual phosphorus excretion.

Bezafibrate reduces heart rate and blood pressure in patients with hypertriglyceridemia.

OBJECTIVE: In hypertriglyceridemic patients, hypertension occurs frequently and may be associated with hyperinsulinemia and elevated plasma levels of free fatty acids (FFA). Besides the lipid-lowering effects, fibrates have been shown to reduce blood pressure in hypertensive patients. The present study was undertaken to investigate the effects of bezafibrate on hemodynamics in relation to insulin, FFA, sympathetic activity, renal sodium absorption, cyclic-GMP (cGMP) and endothelin-1 in hypertriglyceridemic patients. SUBJECTS AND METHODS: Hypertriglyceridemic patients (17) were randomized to receive in a double-blind placebo-controlled study bezafibrate or placebo for 6 weeks. At the end of both treatment periods, blood pressure and heart rate were measured automatically. Plasma insulin, FFA, aldosterone, catecholamines, cGMP, endothelin-1 levels and 24 h urine catecholamines and sodium excretion were assessed. RESULTS: Bezafibrate therapy decreased serum triglycerides (-65%, P < 0.001) and hemodynamic parameters: heart rate decreased from 69 to 66/min (P = 0.009), systolic blood pressure from 137 to 132 mmHg (P = 0.01), diastolic blood pressure from 81 to 79 mmHg (P = 0.07) and mean blood pressure from 102 to 99 mmHg (P = 0.06). Bezafibrate therapy reduced FFA and insulin (-55 and -57% respectively, both P < 0.001), while sympathetic activity and renal sodium absorption were not affected. cGMP increased (+17%, P = 0.008), whereas endothelin-1 levels tended to decrease upon bezafibrate therapy (-10%, P = 0.077) CONCLUSION: Bezafibrate reduces heart rate, blood pressure, insulin and FFA in hypertriglyceridemic patients. The hemodynamic effects cannot be attributed to changes in sympathetic activity or renal sodium absorption. Instead, based on the increase in plasma cGMP levels, the bezafibrate-induced hemodynamic effects are most likely to be caused by bezafibrate-induced improvement of endothelial function.

Uricosuric effect of losartan in patients with renal transplants.

BACKGROUND: The aim of the study was to evaluate the uricosuric effect of the angiotensin II receptor antagonist, losartan, in hypertensive patients with renal transplants who are treated with cyclosporin A (CsA). METHODS: Twenty-six patients with stable renal function and hypertension, 16 men and 10 women, median age 47 years (range, 25-63 years), were studied in an open randomized crossover trial, comparing a 2-week control period with a 2-week period of once-daily administration of 50 mg of losartan. The main outcome measurements were fractional excretion of uric acid (FE(uric acid)) based on 24-hr urine collections and plasma uric acid. RESULTS: The median FE(uric acid) was 5.7% (range, 2.4-10.4%) in the control period with a median change of +0.84% (range, -1.15% to +2.77%) in the losartan period (P<0.0002). Plasma uric acid was 0.47 mM (0.29-0.69 mM) in the control period with a change of -0.03 mM (-0.10 to 0.06 mM) in the losartan period (P<0.002). Diastolic blood pressure was 87 mmHg (70-97 mmHg) in the control period with a change of -3 mmHg (-13 to +6 mmHg) in the losartan period (P<0.005). There was no difference in systolic blood pressure between the two study periods. Plasma creatinine was 165 microM (102-356 microM) in the control period with a change of +9 microM (-36 to +60 microM) in the losartan period (P<0.01). Plasma potassium was 4.2 mM (3.0-4.7 mM) in the control period with a change of + 0.2 mM (-0.2 to +0.9 mM) in the losartan period (P<0.0005). CONCLUSIONS: Once-daily administration of 50 mg of losartan in hypertensive CsA-treated patients with renal transplants caused a 17% increase in FE(uric acid) and an 8% fall in plasma uric acid.

Effect of enalapril on the progression of chronic renal failure. A randomized controlled trial.

In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomized in an open study to basic treatment with enalapril or conventional antihypertensive treatment. The patients were followed for at least 2 years or until they needed dialysis. The groups were comparable with respect to age and sex distribution, etiology of renal diseases, initial levels of renal function and arterial blood pressure (BP), and protein intake. The therapeutic goal was a BP of 120 to 140/80 to 90 mm Hg. The GFR, estimated by the plasma clearance of 51Cr-EDTA, was measured every third month, and the individual rate of progression was calculated as the slope of the GFR v time plot. In the enalapril group, the median decline in GFR was -0.20 (range, +0.18 to -7.11) mL/min/1.73 m2/month and in the control group it was -0.31 (+0.01 to -1.97) mL/min/1.73 m2/month (P less than .05). There was no significant difference in blood pressure or plasma lipid levels between the groups. Thus, the progression of moderate to severe chronic nephropathy was slower on a basic treatment with enalapril as compared to conventional antihypertensive therapy.

Angiotensin converting enzyme (ACE) inhibitors and renal function. A review of the current status.

Angiotensin converting enzyme (ACE) inhibitors are well established in the treatment of hypertension and cardiac failure. Experimental studies in rats have suggested that these agents may protect renal function in chronic nephropathy by a mechanism other than simply lowering the systemic blood pressure. In human studies of incipient diabetic nephropathy, worsening of microalbuminuria was prevented during 3 years of ACE inhibition. ACE inhibitors reduce arterial blood pressure in chronic nephropathy, and may cause a fall in glomerular filtration rate. In diabetic nephropathy, proteinuria was reduced by 2 months' treatment with enalapril to less than half of the values obtained in a control group treated with metoprolol. Nonrandomised trials have suggested that ACE inhibitors may slow the deterioration of renal function, but no comparisons with other antihypertensive agents in prospective studies have been published to date. In chronic renal failure, ACE inhibitors may worsen anaemia and hyperkalaemia. Renovascular hypertension can be treated with ACE inhibitors, but the treatment may lead to a compromised renal function. The dosage of these drugs should be reduced in renal failure and therapy should be started cautiously in this setting, with close monitoring of blood pressure, renal function and plasma potassium.

High serum enalaprilat in chronic renal failure.

BACKGROUND: Most angiotensin-converting enzyme (ACE) inhibitors and their metabolites are excreted renally and doses should hence be reduced in renal insufficiency. We studied whether the dosage of enalapril in daily clinical practice is associated with drug accumulation of enalaprilat in chronic renal failure. METHODS: Fifty nine out-patients with plasma creatinine >150 micromol/L and chronic antihypertensive treatment with enalapril were investigated, in a cross-sectional design. RESULTS: Median glomerular filtration rate (GFR) was 23(range 6-60) ml/minute/1.73 m2. The daily dose of enalapril was 10 (2.5-20) mg and the trough serum concentration of enalaprilat was 31.8 (<2.5-584.7)ng/ml. Ninety percent of the patients had higher serum concentrations of enalaprilat than has been reported in subjects with normal kidney function, and a marked elevation of serum enalaprilat was observed in patients with GFR <30 ml/minute. All but three patients had serum ACE activity below the reference range. The ACE genotype did not influence the results. Additional pharmacokinetic studies were done in nine patients in whom GFR was 23 (10-42)ml/minute/1.73 m2. The median clearance of enalaprilat was 28 (16-68) ml/minute and correlated linearly with GFR (r=0.86, p=0.003). Intra-subject day-to-day variation in trough concentrations was 19.7%. CONCLUSION: Patients with chronic renal failure given small or moderately high doses of enalapril may thus have markedly elevated levels of serum enalaprilat. Whether this affords extra renoprotection, or on the contrary may inappropriately impair renal function, is not known, and should be investigated in prospective, controlled studies.

Parvovirus infection causing red cell aplasia and leukopenia in rheumatoid arthritis.

A case of acute parvovirus B19 infection causing fever, anaemia, leukopenia, and red cell aplasia, in a patient with chronic rheumatoid arthritis is described. The patient had received low doses of corticosteroids for several years, and a small dose of methotrexate recently. There was no evidence of haemolytic anaemia, iron deficiency or drug toxicity. Recovery was associated with the development of antibodies against parvovirus B19, and clearance of viraemia as detected by the polymerase chain reaction. Possible mechanisms for the development of leukopenia are discussed, but there was no evidence for haemophagocytosis.

Filum terminale ependymoma revealed by acute cauda equina compression syndrome following intratumoral and spinal subarachnoid hemorrhage in a patient on oral anticoagulants.

A 65 year-old woman with a filum terminale ependymoma is reported, presenting with acute cauda equina compression syndrome due to intratumoural and subsequent spinal subarachnoid hemorrhage (SAH) following therapy with oral anticoagulants. Few cases of spinal ependymoma have been reported with an acute cauda equina compression syndrome as the initial and only symptom, and the unique feature of our patient's anticoagulant status has only been described once in this setting. Although intratumoural hemorrhage is very well known since the myxopapillary variant is unique to the cauda equina and consists of loose connective tissue and numerous small blood vessels that are prone to bleeding, spinal SAH is seldom seen and the different hypotheses about the pathophysiological mechanisms that might promote bleeding still remain unresolved and will be discussed in this paper, as well as the special clinical features of spinal SAH and some diagnostic and therapeutic implications. A review of the literature (Medline search 1983-1993) revealed only 13 cases, including ours, of spinal SAH due to cauda equina ependymoma, and the results of this review together with our findings are described in this paper.

Chronic hepatitis B and neurogenic muscle disease: case report.

A 17 year-old boy with chronic hepatitis B who developed left-sided muscle wasting is reported. When other possible known diseases as the cause of the neurogenic muscle disease were excluded it was hypothesised that there was a relation between the chronic hepatitis B infection and the neurogenic muscle disease. An immunopathogenesis could be explained by the presence of HBsAg in the cerebral spinal fluid.

[Irreversible renal failure during treatment with angiotensin I converting enzyme inhibitor in bilateral renal stenosis]. / Irreversibel nyreinsufficiens under behandling med angiotensin I konverterende enzymhaemmer ved bilateral nyrearteriestenose.

A case of irreversible renal failure during treatment with enalapril in bilateral renal artery stenosis is described. In the use of converting enzyme inhibitors, caution and monitoring of renal function during treatment is advised.

[Living-donor kidney transplantation]. / Nyretransplantation med levende donor.

In recent years transplantation from living donors has accounted for 25-30% of all kidney transplants in Denmark corresponding to 40-45 per year. Most of these living donors are parents or siblings, although internationally an increasing number are unrelated donors. Donor nephrectomy is associated with only few complications. The long-term outcome for kidney donors is good without increase in mortality or risk for development of hypertension and renal failure; proteinuria may be seen. Living kidney transplantation is the optimal treatment of end-stage renal disease with better graft survival than in cadaver transplantation. The ethical and psychological aspects related to transplantation from a living donor are complex and need to be carefully evaluated when this treatment is offered to the patients.