Impact of the COVID-19 pandemic on symptoms of anxiety and depression and health-related quality of life in older patients with chronic kidney disease.

BACKGROUND: Older patients with advanced chronic kidney disease are at increased risk for a severe course of the coronavirus disease-2019 (COVID-19) and vulnerable to mental health problems. We aimed to investigate prevalence and associated patient (demographic and clinical) characteristics of mental wellbeing (health-related quality of life [HRQoL] and symptoms of depression and anxiety) before and during the COVID-19 pandemic in older patients with advanced chronic kidney disease. METHODS: An ongoing Dutch multicentre prospective cohort study enrols patients of ≥70 years with an eGFR < 20 mL/min/1.73m2 from October 2018 onward. With additional questionnaires during the pandemic (May-June 2020), disease-related concerns about COVID-19 and general anxiety symptoms were assessed cross-sectionally, and depressive symptoms, HRQoL, and emotional symptoms longitudinally. RESULTS: The 82 included patients had a median age of 77.5 years (interquartile range 73.9-82.1), 77% were male and none had tested positive for COVID-19. Cross-sectionally, 67% of the patients reported to be more anxious about COVID-19 because of their kidney disease, and 43% of the patients stated that their quality of life was reduced due to the COVID-19 pandemic. Compared to pre-COVID-19, the presence of depressive symptoms had increased (11 to 22%; p = .022) and physical HRQoL declined (M = 40.4, SD = 10.1 to M = 36.1, SD = 10.4; p < .001), particularly in males. Mental HRQoL (M = 50.3, SD = 9.6 to M = 50.4, SD = 9.9; p = .913) and emotional symptoms remained similar. CONCLUSIONS: Older patients with advanced chronic kidney disease suffered from disease-related anxiety about COVID-19, increased depressive symptoms and reduced physical HRQoL during the COVID-19 pandemic. The impact of the pandemic on this vulnerable patient group extends beyond increased mortality risk, and awareness of mental wellbeing is important. TRIAL REGISTRATION: The study is registered at the Netherlands Trial Register (NTR), trial number NL7104. Date of registration: 06-06-2018.

The kidney, subclinical thyroid disease and cardiovascular outcomes in older patients.

OBJECTIVE: Thyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes. METHODS: In total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45-4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45-60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke. RESULTS: Mean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24-1.07) comparing subclinical hyperthyroidism and 0.90 (0.58-1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism). CONCLUSIONS: In this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction.

Regret about the decision to start dialysis: a cross-sectional Dutch national survey.

BACKGROUND: More older patients with end-stage renal disease (ESRD) are starting dialysis. Elderly patients often prefer treatments that focus on quality of life rather than primarily extending life and a substantial group of elderly dialysis patients might regret their decision to start dialysis. Healthcare provider and patient-related factors may be involved. Our objective was to measure the percentage of patients in the Netherlands who regretted their decision to start dialysis. METHODS: Cross-sectional Dutch national survey of dialysis patients. A short questionnaire about age, satisfaction with pre-dialysis education, present treatment, dialysis initiation, regret about decision to start dialysis and key figures in decision-making was developed. RESULTS: A total of 1371 questionnaires were returned for analysis from 28 dialysis units. Of the patients 7.4% regretted their decision to start dialysis, 50.5% reported the nephrologist's opinion to be crucial in decision-making and these patients experienced more regret than those who made the decision themselves (odds ratio, OR: 1.81). When family influenced decision-making more regret was experienced compared with those who decided themselves (OR: 2.73). Older age was associated with less regret (p = 0.02) and higher treatment satisfaction (p < 0.001); 52.8% of participants described dialysis initiation as being sudden. CONCLUSION: The majority of patients did not regret their decision to start dialysis. Older patients were more satisfied with their treatment and felt less regret. The nephrologist's and the family's opinion were directional in decision-making on ESRD treatment options and were associated with more regret, especially in younger patients.

Randomised trial of no hydration vs. sodium bicarbonate hydration in patients with chronic kidney disease undergoing acute computed tomography-pulmonary angiography.

BACKGROUND: Hydration to prevent contrast-induced acute kidney injury (CI-AKI) induces a diagnostic delay when performing computed tomography-pulmonary angiography (CTPA) in patients suspected of having acute pulmonary embolism. AIM: To analyze whether withholding hydration is non-inferior to sodium bicarbonate hydration before CTPA in patients with chronic kidney disease (CKD). METHODS: We performed an open-label multicenter randomized trial between 2009 and 2013. One hundred thirty-nine CKD patients were randomized, of whom 138 were included in the intention-to-treat population: 67 were randomized to withholding hydration and 71 were randomized to 1-h 250 mL 1.4% sodium bicarbonate hydration before CTPA. Primary outcome was the increase in serum creatinine 48-96 h after CTPA. Secondary outcomes were the incidence of CI-AKI (creatinine increase > 25%/> 0.5 mg dL(-1) ), recovery of renal function, and the need for dialysis within 2 months after CTPA. Withholding hydration was considered non-inferior if the mean relative creatinine increase was ≤ 15% compared with sodium bicarbonate. RESULTS: Mean relative creatinine increase was -0.14% (interquartile range -15.1% to 12.0%) for withholding hydration and -0.32% (interquartile range -9.7% to 10.1%) for sodium bicarbonate (mean difference 0.19%, 95% confidence interval -5.88% to 6.25%, P-value non-inferiority < 0.001). CI-AKI occurred in 11 patients (8.1%): 6 (9.2%) were randomized to withholding hydration and 5 (7.1%) to sodium bicarbonate (relative risk 1.29, 95% confidence interval 0.41-4.03). Renal function recovered in 80.0% of CI-AKI patients within each group (relative risk 1.00, 95% confidence interval 0.54-1.86). None of the CI-AKI patients developed a need for dialysis. CONCLUSION: Our results suggest that preventive hydration could be safely withheld in CKD patients undergoing CTPA for suspected acute pulmonary embolism. This will facilitate management of these patients and prevents delay in diagnosis as well as unnecessary start of anticoagulant treatment while receiving volume expansion.

Nurse practitioners improve quality of care in chronic kidney disease: two-year results of a randomised study.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular risk. Here we evaluate whether strict implementation of guidelines aimed at multiple targets with the aid of nurse practitioners (NP) improves management in patients with CKD. METHODS: MASTER PLAN is a randomised controlled clinical trial, performed in nine Dutch hospitals. Patients with CKD (estimated glomerular filtration rate (eGFR) 20-70 ml÷min) were randomised to receive NP support (intervention group (IG)) or physician care (control group (CG)). Patients were followed for a median of five years. Presented data are an interim analysis on risk factor control at two-year follow-up. RESULTS: We included 788 patients (532 M, 256 F), (393 CG, 395 IG), mean (±SD ) age 59 (±13) years, eGFR 38 (±15) ml÷min÷1.73m(2), blood pressure (BP) 138 (±21)÷80 (±11) mmHg. At two years 698 patients (352 IG, 346 CG) could be analysed. IG as compared with CG had lower systolic (133 vs 135 mmHg; p= 0.04) and diastolic BP (77 vs 80 mmHg; p=0.007), LDL cholesterol (2.30 vs 2.45 mmol(-l); p= 0.03), and increased use of ACE inhibitors, statins, aspirin and vitamin D. The intervention had no effect on smoking cessation, body weight, physical activity or sodium excretion. CONCLUSION: In both groups, risk factor management improved. However, changes in BP control, lipid management and medication use were more pronounced in IG than in CG. Lifestyle interventions were not effective. Coaching by NPs thus benefits everyday care of CKD patients. Whether these changes translate into improvement in clinical endpoints remains to be established.

Hospital specific factors affect quality of blood pressure treatment in chronic kidney disease.

BACKGROUND: Blood pressure (BP) is the most important modifiable risk factor for cardiovascular (CV) disease and progression of kidney dysfunction in patients with chronic kidney disease. Despite extensive antihypertensive treatment possibilities, adequate control is notoriously hard to achieve. Several determinants have been identified which affect BP control. In the current analysis we evaluated differences in achieved BP and achievement of the BP goal between hospitals and explored possible explanations. METHODS: At baseline, BP was measured in a supine position with an oscillometric device in 788 patients participating in the MASTER PLAN study. We also retrieved the last measured office BP from the patient records. Additional baseline characteristics were derived from the study database. Univariate and multivariate analyses were performed with general linear modelling using hospital as a random factor. RESULTS: In univariate analysis, hospital was a determinant of the level of systolic and diastolic BP at baseline. Adjustment for patient, kidney disease, treatment or hospital characteristics affected the relation. Yet, in a fully adjusted model, differences between centres persisted with a range of 15 mmHg for systolic BP and 11 mmHg for diastolic BP. CONCLUSION: Despite extensive adjustments, a clinically relevant, statistically significant difference between hospitals was found in standardised BP measurements at baseline of a randomised controlled study. We hypothesise that differences in the approach towards BP control exist at the physician level and that these explain the differences between hospitals.

For love or money? Attitudes toward financial incentives among actual living kidney donors.

Due to lengthening waiting lists for kidney transplantation, a debate has emerged as to whether financial incentives should be used to stimulate living kidney donation. In recent surveys among the general public approximately 25% was in favor of financial incentives while the majority was opposed or undecided. In the present study, we investigated the opinion of living kidney donors regarding financial incentives for living kidney donation. We asked 250 living kidney donors whether they, in retrospect, would have wanted a financial reward for their donation. We also investigated whether they were in favor of using financial incentives in a government-controlled system to stimulate living anonymous donation. Additionally, the type of incentive deemed most appropriate was also investigated. In general almost half (46%) of the study population were positive toward introducing financial incentives for living donors. The majority (78%) was not in favor of any kind of reward for themselves as they had donated out of love for the recipient or out of altruistic principles. Remarkably, 60% of the donors were in favor of a financial incentive for individuals donating anonymously. A reduced premium or free health insurance was the preferred incentive.

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

[Spontaneous renal bleeding in haemodialysis patients]. / Spontane nierbloedingen bij hemodialysepatiënten.

In three women on chronic haemodialysis because of end-stage renal disease who were 40, 59, and 73 years of age respectively, spontaneous renal bleeding was diagnosed. The first two patients presented with acute flank pain and signs of sudden blood loss, the third one had chronic abdominal pain and anaemia. A CT scan demonstrated perirenal bleeding in all three patients and expansion into the retroperitoneal space in the first and third patient. In the latter two patients, acquired renal cysts had been visible during earlier abdominal ultrasound. None of the patients had severe hypertension, but all of them had received medication enhancing bleeding tendency, such as nadroparin, which was administered during haemodialysis. The first and the last patient were treated conservatively and survived. The second patient was haemodynamically unstable and underwent embolisation to stop the bleeding. She died in hospital after fifteen days due to the complications of a cardiac arrest. Abdominal CT or ultrasound is the technique of choice to evaluate patients with end-stage renal disease with loin pain or bleeding. Most of the time, conservative treatment suffices.

[A patient with both cocaine-induced nasal septum destruction and antibodies against anti-neutrophil cytoplasmic antibodies (ANCA); potential confusion with Wegener's disease]. / Een patiënt met neusseptumdestructie door cocaïne en antistoffen tegen cytoplastische antigenen van neutrofiele granulocyten (ANCA); mogelijke verwarring met de ziekte van Wegener.

A 37-year-old male cocaine user presented with continual, sanguinolent nasal obstruction and persistant pain following a nasal operation one year ago. Examination showed crustae, granulations and exposed septal cartilage in the right nasal passage in addition to a considerable septal deviation to the left. No other physical abnormalities were found. A biopsy of the nasal mucosa showed acute necrotic inflammation. The serological examination revealed markedly elevated anti-neutrophil cytoplasmic antibodies (ANCA) titres with positive reactions against proteinase-3, indicating Wegener's disease. Additional testing also showed a positive ANCA reaction for human neutrophil elastase, which made cocaine use a more plausible cause for the nasal abnormalities than Wegener's disease. Treatment consisted of nasal flushing with saline and, for a short period, a nasal tampon with hydrocortisone-oxytetracycline-polymyxin B ointment. However, the patient did, ultimately, develop a septal perforation. Cocaine-induced nasal abnormalities can imitate symptoms that may fit Wegener's disease, including relevant serological ANCA findings.

[Acute occlusion of the renal artery treated by means of rheolytic thrombectomy]. / Acute occlusie van de A. renalis behandeld met reolytische trombectomie.

A 64-year-old woman presented with recurrent infarction of the right kidney. Because of suspected dysfunction of the contralateral kidney, revascularisation of the occluded right renal artery was attempted. Local thrombolysis with urokinase was unrewarding. So-called rheolytic thrombectomy by means of a Hydrolyser was successful in opening the right main renal artery. Although recovery of right renal function was not complete, renal scintigraphy confirmed salvage of most of the right kidney parenchyma.

Hypopituitarism as a late complication of Plasmodium falciparum malaria: a possible relationship?

Plasmodium falciparum infection causes serious symptoms in the acute phase of the illness. Long-term sequelae are less common. In the following case report we describe a patient who developed hypopituitarism after a severe cerebral malaria infection, which was only recognized 17 years thereafter.

Role of glucocorticoid in excretion of an acute potassium load in patients with Addison's disease and panhypopituitarism.

Glucocorticoid (GC) has been shown to stimulate potassium (K) excretion in various conditions, but it is still incompletely resolved whether its presence is essential for the normal K homeostasis. We addressed this question in patients with selective GC deficiency (panhypopituitarism) and with combined GC and mineralocorticoid deficiency (Addison's disease), studied 24 hours after withdrawal of their regular substitution therapy. Compared to data in healthy subjects, both basal K excretion and the kaliuresis after a KCl load (1 mmol/kg body wt orally) were impaired in either patient group (P < 0.05). Physiological cortisol supplementation (20 mg 3 hr prior to test, and 1 mg/hr during test) increased basal K excretion (from 10.6 +/- 1.8 to 19.2 +/- 1.9 mmol/5 hr, P < 0.01) and KCl stimulated kaliuresis (from 47.9 +/- 6.1 to 54.8 +/- 4.7 mmol/5 hr, P = 0.06) to normal levels in panhypopituitarism. Cortisol also improved basal K excretion (from 10.2 +/- 1.5 to 16.9 +/- 3.5 mmol/5 hr, P < 0.05) and KCl-stimulated K excretion (from 31.6 +/- 2.5 to 45.2 +/- 3.8 mmol/5 hr, P < 0.05) in Addison's disease, although KCl-stimulated K excretion remained below normal (P < 0.01). The effects of cortisol on sodium excretion differed between the two patient groups (P < 0.05) in that only in Addison's disease the improved K excretion was associated with sodium retention. Additional experiments with the purely GC compound dexamethasone (0.5 mg 3 hr prior to test, and 0.03 mg/hr during test) in the patients with Addison's disease also improved K excretion (P < 0.05), but without the concomitant sodium retention observed after cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Natriuretic and hypotensive effect of adenosine-1 blockade in essential hypertension.

We studied the effects of a single dose (100 mg orally) and repeated administration (100 mg o.d. for 7 days) of FK453, a novel adenosine-1 receptor antagonist, on renal sodium handling and blood pressure in eight patients with essential hypertension. Within 60 minutes after administration of FK453, sodium excretion increased threefold. This occurred in the absence of a change in renal hemodynamics, assessed from inulin and para-aminohippurate clearance, and was accompanied by increased fractional excretion of lithium, phosphate, and uric acid and by increased excretion of calcium and magnesium. Maximal free water clearance data showed an increase in maximal urine flow and distal delivery term and a decrease in the diluting segment reabsorption term. FK453 also decreased blood pressure and increased heart rate, but this did not occur until about 3 hours after ingestion, that is, when the natriuresis was already over. The natriuretic effect of FK453 was short-lasting, and continued use of FK453 was in fact accompanied by some net sodium retention. Blood pressure on the seventh day before FK453 treatment was not different from blood pressure before administration of the first dose of FK453. Again an acute natriuretic response followed, although less than after the first dose. Changes in intrarenal sodium handling parameters, blood pressure, and heart rate were similar to those seen after the first dose. The natriuretic and hypotensive effects of FK453 indicate that adenosine-1 receptor activity plays a role in the regulation of blood pressure and renal sodium handling in patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute mineralocorticoid and glucocorticoid receptor blockade on the excretion of an acute potassium load in healthy humans.

To examine the role of mineralocorticoid and glucocorticoid in potassium (K) tolerance in healthy humans, we studied the effects of canrenoate, a mineralocorticoid antagonist, and RU486, a glucocorticoid antagonist, on the excretion of a KCl load. Canrenoate (200 mg, iv) or RU486 (400 mg, orally) was administered 150 min before a KCl load (1 mmol/kg BW, orally) in seven healthy males undergoing maximal water diuresis. Clearance studies were extended for 5 h after the KCl load, and the data were compared with time control, KCl load alone, and canrenoate alone. KCl increased K excretion (from 18.8 +/- 2.4 to 63.3 +/- 3.9 mmol/5 h; P < 0.01) and sodium (Na) excretion (from 35.9 +/- 2.1 to 72.9 +/- 6.0 mmol/5 h; P < 0.01). Clearance calculations, based on maximal water diuresis, were compatible with increased distal Na and volume delivery. Canrenoate alone modestly increased basal cumulative NaCl excretion and had no effect on K excretion. However, canrenoate blunted the kaliuresis after the KCl load (51.9 +/- 4.4 mmol/5 h; P < 0.05 compared to KCl alone) and stimulated natriuresis in a complementary way. Clearance data were compatible with diminished distal Na reabsorption and K secretion in response to an undisturbed KCl-induced increase in distal Na delivery. RU486 did not influence the excretion of the KCl load or its effects on renal sodium handling parameters, although effective glucocorticoid receptor blockade was likely to be present in view of the increase in plasma cortisol. These data suggest that in healthy humans, mineralocorticoid activity, but not glucocorticoid activity, is involved in the elimination of a K load. The latter contrasts with data in adrenalectomized animals, in which situation glucocorticoid as well as aldosterone are indispensible for normal K tolerance.

Natriuretic and kaliuretic response to potassium load: modulation by sodium intake.

Potassium (K) loading is followed by a rapid increase in sodium (Na) and K excretion. To evaluate the influence of Na intake on this effect, we studied the acute natriuretic and kaliuretic response to a single oral K load (100 mmol) in six healthy volunteers equilibrated on a 10-, 100-, and 400-mmol Na intake. Compared to the 100-mmol Na intake, the 400-mmol Na intake greatly enhanced the natriuretic effect of the K load; during the 10-mmol Na intake no natriuresis but even some Na retention occurred. The kaliuretic effect was not significantly changed and occurred at similar values of plasma K. Plasma aldosterone was suppressed during the 400-mmol Na diet and stimulated during the 10-mmol Na diet, but the relative increments after the KCl load did not differ among the three diets. In conclusion, whereas the effect of a K load on kaliuresis is relatively independent of Na intake, its effect on Na excretion varies from marked natriuresis to slight Na retention. The Na retention is probably due to acute K-induced aldosterone stimulation, and the natriuresis to K-induced increase in distal Na delivery not utilized to promote K excretion. Apparently, the integration of renal Na and K handling after a K load is such that K balance is maintained at the cost of Na balance.

Short-term indomethacin administration does not impair excretion of acute potassium load in humans.

Maintenance treatment with prostaglandin synthesis inhibitors often causes some degree of hyperkalemia, indicating impaired potassium (K) excretion. Hypoaldosteronism probably is a mediating factor, but it is unknown whether these drugs also impair renal K excretion directly. Indomethacin, for example, stimulates NaCl reabsorption in Henle's loop, and thus may impair K excretion by decreasing distal NaCl delivery. We therefore studied the effect of 1 day administration of indomethacin (50 mg tid) on the excretion of a single oral KCl (1 mmol kg-1 body weight) in six healthy volunteers taking a 40 mmol sodium diet. To allow analysis of renal sodium handling, clearance studies were performed during water loading. In this acute setting, indomethacin had no effect on plasma K, and did not decrease plasma aldosterone. However, indomethacin clearly reduced NaCl excretion. Nonetheless, the excretion of the K load was entirely normal. Excretion of the K load was accompanied by increased clearance of phosphate and uric acid, and natriuresis. Data derived from the maximal free water clearance were compatible with increased delivery to and decreased reabsorption from the diluting segment. Occurrence of these effects was not prevented by indomethacin, although overall NaCl excretion remained less than observed without indomethacin. Indomethacin reduced prostaglandin E2 excretion substantially. Apparently, in normal man indomethacin does not impair K excretion directly, even though it greatly reduces NaCl excretion. Moreover, the effects of K on renal NaCl handling, probably contributing to the excretion of a K load, are not dependent on renal prostaglandins.