Zietse, R.

Hyponatremia and bone: An emerging relationship (Article)

2012-01-01T00:00:00Z

Hyponatremia is the most common electrolyte disorder and is mainly known for its neurological complications. New studies suggest previously unrecognized complications of hyponatremia, including falls, osteoporosis and fractures. Because these novel associations are mainly derived from epidemiological studies, it remains unclear whether hyponatremia has a direct effect on bone or whether it is a surrogate marker of another etiology. However, one animal and one in vitro study now show that hyponatremia can have direct effects on bone, mainly via activation of osteoclasts. The association between hyponatremia and fractures appears to be independent of osteoporosis (defined as low BMD). Also, data suggest that this association cannot be fully explained by the possibility that hyponatremia predisposes to falls. Hyponatremia, therefore, also has an effect on bone quality that is not captured by BMD. Here, the emerging relationship between hyponatremia and bone is reviewed, with special emphasis on possible mechanisms, unanswered questions and clinical implications.

Mild hyponatremia as a risk factor for fractures: The rotterdam study (Article)

2011-08-01T00:00:00Z

Recent studies suggest that mild hyponatremia is associated with fractures, but prospective studies are lacking. We studied whether hyponatremia is associated with fractures, falls, and/or bone mineral density (BMD). A total of 5208 elderly subjects with serum sodium assessed at baseline were included from the prospective population-based Rotterdam Study. The following data were analyzed: BMD, vertebral fractures (mean follow-up 6.4 years), nonvertebral fractures (7.4 years), recent falls, comorbidity, medication, and mortality. Hyponatremia was detected in 399 subjects (7.7%, 133.4±2.0mmol/L). Subjects with hyponatremia were older (73.5±10.3 years versus 70.0±9.0 years, p<.001), had more recent falls (23.8% versus16.4%, p<.01), higher type 2 diabetes mellitus prevalence (22.2% versus 10.3%, p<.001), and more often used diuretics (31.1% versus 15.0%, p<.001). Hyponatremia was not associated with lower BMD but was associated with increased risk of incident nonvertebral fractures [hazard ratio (HR) =1.39, 95% confidence interval (CI) 1.11-1.73, p=.004] after adjustment for age, sex, and body mass index. Further adjustments for disability index, use of diuretics, use of psycholeptics, recent falls, and diabetes did not modify results. In the fully adjusted model, subjects with hyponatremia also had increased risk of vertebral fractures at baseline [odds ratio (OR)=1.78, 95% CI 1.04-3.06, p=.037] but not at follow-up. Finally, all-cause mortality was higher in subjects with hyponatremia (HR=1.21, 95% CI 1.03-1.43, p=.022). It is concluded that mild hyponatremia in the elderly is associated with an increased risk of vertebral fractures and incident nonvertebral fractures but not with BMD. Increased fracture risk in hyponatremia also was independent of recent falls, pointing toward a possible effect on bone quality. Copyright

The authors reply: (Article)

2011-06-01T00:00:00Z

Potential deleterious effects of vasopressin in chronic kidney disease and particularly autosomal dominant polycystic kidney disease (Article)

2011-06-01T00:00:00Z

The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of vasopressin activity reduces proteinuria, renal hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis in animal models. The potential detrimental influence of vasopressin is probably mediated by its effects on mesangial cell proliferation, renin secretion, renal hemodynamics, and blood pressure. In this review, we discuss the increasing body of evidence pointing towards the contribution of vasopressin to chronic kidney disease progression in general and to autosomal dominant polycystic kidney disease in particular. These data allude to the possibility that interventions directed at lowering vasopressin activity, for example by the administration of vasopressin receptor antagonists or by drinking more water, may be beneficial in chronic kidney disease. Copyright

Unexplained hyponatremia: Seek and you will find (Article)

2011-06-01T00:00:00Z

Background: Hyponatremia is a common diagnostic challenge. Methods: An index case is presented to discuss the diagnostic approach to chronic and unexplained hyponatremia. Results: The index case concerns a 60-year-old man with chronic hepatitis C and previous alcohol use who was referred because of weight loss, poor dietary intake, dizzy spells, and unexplained hyponatremia (serum sodium 124-129 mmol/l). A low urine sodium concentration (20 mmol/l) and a lowfractional sodium excretion (0.07%) were observed repeatedly, while urine osmolality washigh (>400 mosm/kg). The central questions in this case are: what is the differential diagnosis, which tests are needed to confirm or exclude a diagnosis, and how would you proceed if no obvious cause is found? Conclusions: The diagnosis of this case of unexplained hyponatremia was unexpected, but important because it was treatable. The challenges and caveats of the diagnostic approach to hyponatremia are discussed. A diagnostic algorithm to guide clinicians who are confronted with similar cases is presented. Copyright

Justification for a home-based education programme for kidney patients and their social network prior to initiation of renal replacement therapy (Article)

2011-05-30T00:00:00Z

In this article, an ethical analysis of an educational programme on renal replacement therapy options for patients and their social network is presented. The two main spearheads of this approach are: (1) offering an educational programme on all renal replacement therapy options ahead of treatment requirement and (2) a homebased approach involving the family and friends of the patient. Arguments are offered for the ethical justification of this approach by considering the viewpoint of the various stakeholders involved. Finally, reflecting on these ethical considerations, essential conditions for carrying out such a programme are outlined. The goal is to develop an ethically justified and responsible educational programme.

Risk factors associated with encapsulating peritoneal sclerosis in Dutch EPS study (Article)

2011-05-01T00:00:00Z

Objective: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD) with a multifactorial pathophysiology and possible increasing incidence. The aim of the present study was to evaluate the independent associations of PD duration, age, dialysis fluids, and kidney transplantation with EPS. Methods: A multicenter case-control study was performed in the Netherlands from 1 January 1996 until 1 July 2007. The population comprised 63 patients with EPS and 126 control patients. Control patients were selected from the national registry and were matched for date of PD start. Associations were analyzed using a log linear regression model. Primary outcome was appearance of EPS. Results: Compared with control patients, patients with EPS were younger at the start of PD (34.7 ±15.4 years vs. 51.5± 14.7 years, p < 0.0001). The cumulative period on PD was longer in EPS patients than in control patients (78.7 ± 37.8 months vs. 32.8 ±24 months, p < 0.0001), and the cumulative period on icodextrin was also longer in EPS patients (32.7 ±23.3 months vs. 18.1 ±15.7 months, p = 0.006). Compared with control patients, more EPS patients underwent kidney transplantation (47 vs. 59, p< 0.0001). With regard to the period after transplantation, the yearly probability of EPS increased in the year after transplantation to 7.5% from 1.75%. In multivariate regression analysis, cumulative PD duration, age at PD start, transplantation, time from last transplantation to EPS, calendar time, time on icodextrin, and ultrafiltration failure were independently associated with EPS. Transfer from PD to hemodialysis for reasons other than suspected EPS could not be identified as a risk factor for EPS. Conclusions: Duration of PD, age at PD start, kidney transplantation, time since last transplantation, ultrafiltration failure, and time on icodextrin were associated with a higher risk of EPS.

Hyponatremia and mortality: How innocent is the bystander? (Article)

2011-05-01T00:00:00Z

Hyponatremia and inflammation: The emerging role of interleukin-6 in osmoregulation (Article)

2011-05-01T00:00:00Z

Although hyponatremia is a recognized complication of several inflammatory diseases, its pathophysiology in this setting has remained elusive until recently. A growing body of evidence now points to an important role for interleukin-6 in the non-osmotic release of vasopressin. Here, we review this evidence by exploring the immuno-neuroendocrine pathways connecting interleukin-6 with vasopressin. The importance of these connections extends to several clinical scenarios of hyponatremia and inflammation, including hospital-acquired hyponatremia, postoperative hyponatremia, exercise-associated hyponatremia, and hyponatremia in the elderly. Besides insights in pathophysiology, the recognition of the propensity for antidiuresis during inflammation is also important with regard to monitoring patients and selecting the appropriate intravenous fluid regimen, for which recommendations are provided. Copyright

A case of primary aldosteronism revealed after renal transplantation (Article)

2010-11-23T00:00:00Z

Background. A 57-year-old woman was referred to a nephrology clinic because of chronic hypokalemia. She had a history of polycystic kidney disease, resistant hypertension, atrial fibrillation, type 2 diabetes, stroke, and end-stage renal disease, and had received a kidney transplant from a deceased donor at the age of 48 years. At presentation, the patient described symptoms of chronic fatigue and muscle aches, but she did not report pareses. Her medications included four antihypertensive agents, glucose-lowering drugs, immunosuppressants, digoxin, a coumarin derivative, and potassium chloride.Investigations. Full history, physical examination, laboratory testing of blood and urine, including aldosterone-torenin ratio, and a saline infusion test.Diagnosis. Primary aldosteronism.Management. Treatment with spironolactone resulted in prompt control of hypertension and hypokalemia, allowing discontinuation of potassium chloride and reduction in antihypertensive medication.

Angiotensin II induces phosphorylation of the thiazide-sensitive sodium chloride cotransporter independent of aldosterone (Article)

2010-08-18T00:00:00Z

We studied here the independent roles of angiotensin II and aldosterone in regulating the sodium chloride cotransporter (NCC) of the distal convoluted tubule. We adrenalectomized three experimental and one control group of rats. Following surgery, the experimental groups were treated with either a high physiological dose of aldosterone, a non-pressor, or a pressor dose of angiotensin II for 8 days. Aldosterone and both doses of angiotensin II lowered sodium excretion and significantly increased the abundance of NCC in the plasma membrane compared with the control. Only the pressor dose of angiotensin II caused hypertension. Thiazides inhibited the sodium retention induced by the angiotensin II non-pressor dose. Both aldosterone and the non-pressor dose of angiotensin II significantly increased phosphorylation of NCC at threonine-53 and also increased the intracellular abundance of STE20/SPS1-related, proline alanine-rich kinase (SPAK). No differences were found in other modulators of NCC activity such as oxidative stress responsive protein type 1 or with-no-lysine kinase 4. Thus, our in vivo study shows that aldosterone and angiotensin II independently increase the abundance and phosphorylation of NCC in the setting of adrenalectomy; effects are likely mediated by SPAK. These results may explain, in part, the hormonal control of renal sodium excretion and the pathophysiology of several forms of hypertension.Kidney International advance online publication, 18 August 2010; doi:10.1038/ki.2010.290.

A Case Series of Proton Pump Inhibitor-Induced Hypomagnesemia (Article)

2010-07-01T00:00:00Z

Proton pump inhibitor (PPI)-induced hypomagnesemia has been recognized since 2006. Our aim was to further characterize the clinical consequences and possible mechanisms of this electrolyte disorder using 4 cases. Two men (aged 63 and 81 years) and 2 women (aged 73 and 62 years) had been using a PPI (esomeprazole, pantoprazole, omeprazole, and rabeprazole, 20-40 mg) for 1-13 years. They developed severe hypomagnesemia (magnesium, 0.30 ± 0.28 mEq/L; reference, 1.40-2.10 mEq/L) with hypocalcemia (calcium, 6.4 ± 1.8 mg/dL), relative hypoparathyroidism (parathyroid hormone, 43 ± 6 pg/mL), and extremely low urinary calcium and magnesium excretion. One patient was admitted with postanoxic encephalopathy after a collapse likely caused by arrhythmia. The others had electrocardiogram abnormalities (prolonged QT interval, ST depression, and U waves). Concomitant hypokalemia (potassium, 2.8 ± 0.1 mEq/L) was considered the trigger for these arrhythmias. Hypomagnesemia-induced kaliuresis (potassium excretion, 65 ± 24 mEq/L) was identified as the cause of hypokalemia. This series of PPI-induced hypomagnesemia shows that this is a generic effect. It also indicates that hypomagnesemia may occur within 1 year of PPI therapy initiation and can have serious clinical consequences, likely triggered by the associated hypokalemia. A high index of suspicion is required in PPI users for unexplained hypomagnesemia, hypocalcemia, hypokalemia, or associated symptoms.

Vasopressin-receptor antagonists (Article)

2010-07-01T00:00:00Z

Despite a crucial role in body fluid homeostasis, elevated vasopressin levels can also be pathological in conditions such as congestive heart failure, liver cirrhosis and the syndrome of inappropriate antidiuretic hormone secretion. The result of elevated vasopressin is renal water retention and hyponatremia, a low serum sodium concentration. Hyponatremia is associated with excess morbidity and mortality. Nonpeptide vasopressin-receptor antagonists represent a new drug class of small molecules that competitively inhibit one or more of the vasopressin receptors. There are three vasopressin receptors in humans, including V1a, V1b and V2. Selective V2- and combined V1a/V2-receptor antagonists have been developed for the treatment of hyponatremia resulting from congestive heart failure, liver cirrhosis and the syndrome of inappropriate antidiuretic hormone secretion. Two nonpeptide vasopressin-receptor antagonists, conivaptan and tolvaptan, have recently been approved by American and European drug authorities for clinical use. This article aims to provide a succinct and clinical update on nonpeptide vasopressin-receptor antagonists, including their mechanism of action, performance in randomized clinical trials and current clinical status.

Diagnostic value of urinary dysmorphic erythrocytes in clinical practice (Article)

2010-07-01T00:00:00Z

Background: In clinical practice, discriminating between glomerular and nonglomerular causes of hematuria is often difficult. Dysmorphic red blood cells (dRBC) in the urinary sediment are claimed to be effective, but the cutoff points in the literature vary. This follow-up study aimed to determine the diagnostic value of dRBC. Methods: We investigated 134 hematuria patients in the departments of nephrology and urology. To diagnose the origin of hematuria, urological and/or nephrological examination was performed and the %dRBC identified by microscopy. Follow-up was performed after 3.5 years. Results: The cause of hematuria was proven in 68 patients (35% glomerular; 65% nonglomerular). Patients with glomerular disease had significantly more albuminuria and dRBC than patients with nonglomerular disease, but the %dRBC ranged from 1 to 50% and no optimal cutoff could be identified. Logistic regression analysis showed that %dRBC had a predicted probability to diagnose glomerular disease of 77.9% (area under the curve, AUC, 0.85). When %dRBC was combined with other risk factors such as serum creatinine, sex, age, dipstick erythrocyte or proteinuria score and number of casts, the predictive probability increased to 90.6% (AUC 0.97). Follow-up of the included patients showed no benefit of dRBC to identify patients at risk for glomerular disease. Conclusions: The diagnostic value of routinely collected urinary dRBC to diagnose glomerular disease in patients presenting with hematuria is modest. However, including dRBC with other variables, such as age and erythrocyte score on dipstick testing may increase the sensitivity, but needs to be confirmed in another, preferably larger, population. Copyright

Water balance disorders after neurosurgery: The triphasic response revisited (Article)

2010-02-01T00:00:00Z

Water balance disorders after neurosurgery are well recognized, but detailed reports of the triphasic response are scarce. We describe a 55-year-old woman, who developed the triphasic response with severe hyper- and hyponatraemia after resection of a suprasellar meningioma. The case illustrates how sudden and dramatic the changes in water balance after neurosurgery can be. The biochemical profile suggested central diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion. The underlying pathophysiology was further analysed using fractional excretions, measurements of renin, aldosterone and vasopressin and a metyrapone test. Diagnostic, therapeutic and preventive strategies for these intriguing but complex cases are proposed.

Inhibiting renal sodium-glucose transport in diabetes: Pass the salt (Article)

2009-12-01T00:00:00Z

Osmomediated natriuresis in humans: The role of vasopressin and tubular calcium sensing (Article)

2009-11-01T00:00:00Z

Background. The aim was to investigate the unknown mechanism of osmomediated natriuresis. This is the phenomenon by which hypertonic saline (HS) produces a larger natriuresis than isotonic saline (IS), despite the same sodium content.Methods. Seven healthy volunteers first received HS and then IS (both 3.85 mmol sodiumkg). To investigate the role of calcium metabolism, four patients received HS, two with an activating mutation (ADH) and two with an inactivating mutation (FHH) of the calcium-sensing receptor (CaSR).Results. In healthy volunteers, HS produced mild hypernatraemia, a 4-fold rise in vasopressin (to 2.2 ± 0.85 pgmL) and a 3-fold rise in natriuresis compared with a 1.5-fold rise with IS (P = 0.002). This confirmed osmomediated natriuresis. HS caused calciuresis to increase 1.4-fold and then reduced it 1.4-fold, whereas IS failed to increase calciuresis and caused it to fall 3.7-fold (P = 0.05). Natriuresis and calciuresis in ADH patients were similar to healthy volunteers receiving HS, whereas a blunted response was seen in FHH patients. Patient vasopressin levels did not exceed 1.3 pgmL and changes from baseline were variable. In one FHH patient, a 3-fold rise in vasopressin did not prevent the blunted natriuresis and calciuresis. In one ADH patient, natriuresis and calciuresis were similar to healthy volunteers despite a 1.7-fold fall in vasopressin.Conclusions. Our data suggest that not only vasopressin (possibly via its V1a receptor), but also the CaSR (which is sensitive to high sodium concentrations) may play a role in osmomediated natriuresis. These results shed new light on osmomediated natriuresis and suggest roles for the CaSR beyond calcium regulation.

Fluid, electrolyte and acid-base disorders associated with antibiotic therapy (Article)

2009-04-01T00:00:00Z

Antibiotics are among the most frequently prescribed drugs in medicine. Their use, however, is often limited by associated renal toxic effects. The most common manifestation of these toxic effects is decreased glomerular filtration rate. However, they can also occur while renal function remains near to normal. This Review focuses on antibiotic-associated fluid, electrolyte and acid-base disorders that do not greatly reduce glomerular filtration. Renal tubules can be affected by antibiotics at various locations. In the proximal tubule, toxic effects of tetracyclines and aminoglycosides can result in complete proximal tubular dysfunction, also known as Fanconi syndrome. Aminoglycosides (and capreomycin) can also affect the loop of Henle and lead to a Bartter-like syndrome. In the collecting ducts, antibiotics can cause a diverse range of disorders, including hyponatremia, hypokalemia, hyperkalemia, renal tubular acidosis, and nephrogenic diabetes insipidus. Causative antibiotics include trimethoprim, amphotericin B, penicillins, ciprofloxacin, demeclocycline and various antitubercular agents. Here, we describe the mechanisms that disrupt renal tubular function. Integrated with the physiology of each successive nephron segment, we discuss the receptors, transporters, channels or pores that are affected by antibiotics. This insight should pave the way for pathophysiology-directed treatment of these disorders.

The renal WNK kinase pathway: A new link to hypertension (Article)

2009-04-01T00:00:00Z

Delirium due to a drug-drug interaction of lithium and an NSAID (Article)

2009-03-01T00:00:00Z

Delirium due to a drug-drug interaction of lithium and an NSAID (Article)

2009-01-01T00:00:00Z

Reply (Article)

2008-12-01T00:00:00Z

Severe hypokalaemia caused by flucloxacillin (Article)

2008-06-01T00:00:00Z

Hypernatraemia in critically ill patients: Too little water and too much salt (Article)

2008-05-01T00:00:00Z

Background. Our objective was to study the risk factors and mechanisms of hypernatraemia in critically ill patients, a common and potentially serious problem. Methods. In 2005, all patients admitted to the medical, surgical or neurological intensive care unit (ICU) of a university hospital were reviewed. A 1:2 matched case-control study was performed, defining cases as patients who developed a serum sodium ≥150 mmol/l in the ICU. Results. One hundred and thirty cases with ICU-acquired hypernatraemia (141 ± 3 to 156 ± 6 mmol/l) were compared to 260 controls. Sepsis (9% versus 2%), hypokalaemia (53% versus 34%), renal dysfunction (53% versus 13%), hypoalbuminaemia (91% versus 55%), the use of mannitol (10% versus 1%) and use of sodium bicarbonate (23% versus 0.4%) were more common in cases (P < 0.05 for all) and were independently associated with hypernatraemia. During the development of hypernatraemia, fluid balance was negative in 80 cases (-31 ± 2 ml/kg/day), but positive in 50 cases (72 ± 3 ml/kg/day). Cases with a positive fluid balance received more sodium plus potassium (148 ± 2 versus 133 ± 3 mmol/l, P < 0.001). On average, cases were polyuric (40 ± 5 ml/kg). Mortality was higher in cases (48% versus 10%, P < 0.001), for which hypernatraemia was an independent predictor (odds ratio 4.3, 95% confidence interval 2.5 to 7.2). Conclusions. Hypernatraemia seems to develop in the ICU because various factors promote renal water loss, which is then corrected with too little water or overcorrected with relatively hypertonic fluids. Therapy should therefore rely on adding electrolyte-free water and/or creating a negative sodium balance. Adjustments in intravenous fluid regimens may prevent hypernatraemia.

Hyponatremia revisited: Translating physiology to practice (Article)

2008-04-01T00:00:00Z

The complexity of hyponatremia as a clinical problem is likely caused by the opposite scenarios that accompany this electrolyte disorder regarding pathophysiology (depletional versus dilutional hyponatremia, high versus low vasopressin levels) and therapy (rapid correction to treat cerebral edema versus slow correction to prevent osmotic demyelination, fluid restriction versus fluid resuscitation). For a balanced differentiation between these opposites, an understanding of the pathophysiology of hyponatremia is required. Therefore, in this review an attempt is made to translate the physiology of water balance regulation to strategies that improve the clinical management of hyponatremia. A physiology-based approach to the patient with hyponatremia is presented, first addressing the possibility of acute hyponatremia, and then asking if and if so why vasopressin is secreted non-osmotically. Additional diagnostic recommendations are not to rely too heavily of the assessment of the extracellular fluid volume, to regard the syndrome of inappropriate antidiuresis as a diagnosis of exclusion, and to rationally investigate the pathophysiology of hyponatremia rather than to rely on isolated laboratory values with arbitrary cutoff values. The features of the major hyponatremic disorders are discussed, including diuretic-induced hyponatremia, adrenal and pituitary insufficiency, the syndrome of inappropriate antidiuresis, cerebral salt wasting, and exercise-associated hyponatremia. The treatment of hyponatremia is reviewed from simple saline solutions to the recently introduced vasopressin receptor antagonists, including their promises and limitations. Given the persistently high rates of hospital-acquired hyponatremia, the importance of improving the management of hyponatremia seems both necessary and achievable. Copyright

Hypokalaemia and subsequent hyperkalaemia in hospitalized patients (Article)

2007-12-01T00:00:00Z

Background. The objective was to study the epidemiology of hypokalaemia [serum potassium concentration (SK) <3.5 mmol/l] in a general hospital population, specifically focusing on how often and why patients develop subsequent hyperkalaemia (SK<5.0 mmol/l). Methods. In a 3-month hospital-wide study we analysed factors contributing to hypokalaemia and subsequent hyperkalaemia. Results. From 1178 patients in whom SKwas measured, 140 patients (12%) with hypokalaemia were identified (SK3.0 ± 0.3 mmol/l). One hundred patients (71%) had hospital-acquired hypokalaemia. Common causes of hypokalaemia included gastrointestinal losses (67%), diuretics (36%) and haematological malignancies (9%). In 104 patients (74%), hypokalaemia was multifactorial. Hypokalaemia frequently coexisted with hyponatraemia (24%) and, when measured, hypomagnesaemia (61%). Twenty-three patients (16%) developed hyperkalaemia (highest SK5.7 ± 0.7 mmol/l) following hypokalaemia. In these patients, potassium suppletion was not more common (70 vs 59%, P = 0.5), but when potassium was given, the total amount administered was significantly higher (median 350 mmol vs 180 mmol, P = 0.02). Furthermore, these patients more often received total parenteral nutrition (17 vs 4%, P = 0.02) and magnesium suppletion (30 vs 9%, P = 0.009), and more often had haematological malignancies (22 vs 6%, P = 0.03). Conclusions. Hypokalaemia is a multifactorial and usually hospital-acquired condition associated with hyponatraemia and hypomagnesaemia. One out of every six patients with hypokalaemia developed subsequent hyperkalaemia. Besides potassium suppletion, total parenteral nutrition (source of potassium), magnesium suppletion (may reduce kaliuresis) and haematological malignancy (may cause cell lysis) contribute to hyperkalaemia following hypokalaemia. Caution with potassium suppletion and frequent monitoring of SKmay prevent iatrogenic hyperkalaemia.

Seropositivity for cytomegalovirus in patients with end-stage renal disease is strongly associated with atherosclerotic disease (Article)

2007-11-01T00:00:00Z

Background. Infection with cytomegalovirus (CMV) is considered a risk factor for progression of atherosclerotic disease. Patients with end-stage renal disease (ESRD) display signs of frequent CMV re-activation, which may be caused by the uraemia-associated defect in cellular immunity. The possible contribution of CMV seropositivity to the hugely increased risk for cardiovascular disease in patients with ESRD is not clear. Methods. In a retrospective study we analysed the clinical data of patients with ESRD that were evaluated for renal transplantation from January 2002 to March 2006. Classical cardiovascular risk factors and CMV seropositivity were related to the prevalence of atherosclerotic disease. Results. A total of 408 patients were evaluated with a median age of 52 years (range 18-81 years). Multivariate logistic regression identified age (odds ratio; OR 2.7 per decade), smoking (OR 2.2), hypertension (OR 1.9), C-reactive protein (CRP) (OR 2.6) and CMV seropositivity (OR 2.7) as independent variables that were significantly associated with a positive medical history of atherosclerotic disease. The average titre for anti-CMV immunoglobulin G was higher in patients with atherosclerotic disease (100 AU/ml vs 71 AU/ml, P < 0.05). CMV seropositivity was independently associated with an elevated CRP. In addition, patients with the combination of a high CRP and CMV seropositivity showed the highest prevalence of atherosclerotic disease. Conclusion. CMV seropositivity is significantly associated with atherosclerotic disease in ESRD patients. Our data suggest that the risk for progressive atherosclerosis is specifically increased in patients with an inflammatory response to CMV.

Increasing incidence of severe encapsulating peritoneal sclerosis after kidney transplantation [10] (Article)

2007-08-01T00:00:00Z

Preventing a Drop in Effective Plasma Osmolality to Minimize the Likelihood of Cerebral Edema During Treatment of Children with Diabetic Ketoacidosis (Article)

2007-05-01T00:00:00Z

Objectives: To test whether a drop in effective plasma osmolality (PEff osm; 2 × plasma sodium [PNa] + plasma glucose concentrations) during therapy for diabetic ketoacidosis (DKA) is associated with an increased risk of cerebral edema (CE), and whether the development of hypernatremia to prevent a drop in the PEff osmis dangerous. Study design: This study is a retrospective comparison of a CE group (n = 12) and non-CE groups with hypernatremia (n = 44) and without hypernatremia (n = 13). Results: The development of CE (at 6.8 ± 1.5 hours) was associated with a drop in PEff osmfrom 304 ± 5 to 290 ± 5 mOsm/kg (P < .001). Control patients did not show this drop in PEff osmat 4 hours (1 ± 2 and 2 ± 2 vs -9 ± 2 mOsm/kg; P < .01), because of a larger rise in PNaand/or a smaller drop in plasma glucose. During this period, the CE group received more near-isotonic fluids (69 ± 9 vs 35 ± 2 and 27 ± 3 mL/kg; P < .001). The CE group had a higher mortality (3/12 vs 0/57; P = .003), and more neurologic sequelae (5/12 vs 1/57; P < .001). Conclusions: CE during therapy for DKA was associated with a drop in PEff osm. An adequate rise in PNamay be needed to prevent this drop in PEff osm.

Novel risk factors for hospital-acquired hyponatraemia: A matched case-control study (Article)

2007-03-01T00:00:00Z

Background: Hospital-acquired hyponatraemia is a common and potentially serious condition. Risk factors for hospital-acquired hyponatraemia have not been studied in a controlled fashion. Methods: From 1501 patients in whom serum sodium (SNa) was determined, 50 cases with hospital-acquired hyponatraemia (in-hospital decrease in SNa≥ 7 mmol/l to < 136 mmol/l) were identified. They were matched by age, gender and department to 69 normonatraemic controls. Results: In the 50 cases, SNafell from 141 ± 2 to 130 ± 4 mmol/l, while controls remained normonatraemic. During the development of hyponatraemia, C-reactive protein (CRP) increased in cases (median from 23 to 146 mg/l), whereas it decreased in controls (median from 31 to 24 mg/l, P = 0.008). Additional factors associated with hospital-acquired hyponatraemia included diabetes mellitus (16/50 vs. 10/69, P = 0.009) and the use of insulin (12/50 vs. 4/69, P = 0.007), antibiotics (41/50 vs. 38/69, P = 0.006) and opioids (32/50 vs. 27/69, P = 0.005). Multivariate conditional logistic regression showed that the use of insulin [odds ratio (OR) 10.5, 95% confidence interval (CI) 1.5-72.4], antibiotics (OR 4.5, 95% CI 1.4-14.6) and opioids (OR 2.9, 95% CI 1.1-7.8) was also independently associated with hospital-acquired hyponatraemia. Mortality (6/50 vs. 1/69, P = 0.04) and intensive care admission (15/50 vs. 7/69, P = 0.008) were higher in cases. Conclusions: An increase in CRP and the use of insulin, antibiotics and opioids are novel risk factors for hospital-acquired hyponatraemia. These factors represent interesting new clues regarding the pathophysiology of hospital-acquired hyponatraemia, suggesting that the acute-phase response, pain and/or direct drug effects could be involved in the release of antidiuretic hormone.

Combined renal tubular acidosis and diabetes insipidus in hematological disease (Article)

2007-03-01T00:00:00Z

Background: A 39-year-old male with multiple myeloma was admitted for treatment with melphalan and autologous stem cell reinfusion. He presented with hypokalemia and hyperchloremic non-anion-gap metabolic acidosis with a high urinary pH. He also had hypomagnesemia, hypophosphatemia, hypouricemia, proteinuria and glucosuria. The patient subsequently developed polyuria with a low urine osmolality, hypernatremia and, finally, acute renal failure. Investigations: Physical examination, blood and urine analyses, kidney biopsy and tonicity balance. Diagnosis: Fanconi syndrome with proximal (type II) renal tubular acidosis caused by myeloma kidney. Renal tubular acidosis was complicated by probable nephrogenic diabetes insipidus and acute renal failure. Management: Potassium supplementation, sodium bicarbonate therapy, intravenous fluid therapy and dialysis.

Preload dependence of new Doppler techniques limits their utility for left ventricular diastolic function assessment in hemodialysis patients (Article)

2003-01-01T00:00:00Z

Left ventricular (LV) hypertrophy leads to diastolic dysfunction. Standard Doppler transmitral and pulmonary vein (PV) flow velocity measurements are preload dependent. New techniques such as mitral annulus velocity by Doppler tissue imaging (DTI) and LV inflow propagation velocity measured from color M-mode have been proposed as relatively preload-independent measurements of diastolic function. These parameters were studied before and after hemodialysis (HD) with ultrafiltration to test their potential advantage for LV diastolic function assessment in HD patients. Ten patients (seven with LV hypertrophy) underwent Doppler echocardiography 1 h before, 1 h after, and 1 d after HD. Early (E) and atrial (A) peak transmitral flow velocities, peak PV systolic (s) and diastolic (d) flow velocities, peak e and a mitral annulus velocities in DTI, and early diastolic LV flow propagation velocity (V(p)) were measured. In all patients, the E/A ratio after HD (0.54; 0.37 to 1.02) was lower (P < 0.01) than before HD (0.77; 0.60 to 1.34). E decreased (P < 0.01), whereas A did not. PV s/d after HD (2.15; 1.08 to 3.90) was higher (P < 0.01) than before HD (1.80; 1.25 to 2.68). Tissue e/a after HD (0.40; 0.26 to 0.96) was lower (P < 0.01) than before HD (0.56; 0.40 to 1.05). Tissue e decreased (P < 0.02), whereas a did not. V(p) after HD (30 cm/s; 16 to 47 cm/s) was lower (P < 0.01) than before HD (45 cm/s; 32 to 60 cm/s). Twenty-four hours after the initial measurements values for E/A (0.59; 0.37 to 1.23), PV s/d (1.85; 1.07 to 3.38), e/a (0.41; 0.27 to 1.06), and V(p) (28 cm/s; 23 to 33 cm/s) were similar as those taken 1 h after HD. It is concluded that, even when using the newer Doppler techniques DTI and color M-mode, pseudonormalization, which was due to volume overload before HD, resulted in underestimation of the degree of diastolic dysfunction. Therefore, the advantage of these techniques over conventional parameters for the assessment of LV diastolic function in HD patients is limited. Assessment of LV diastolic function should not be performed shortly before HD, and its time relation to HD is essential.

Specific effect of the infusion of glucose on blood volume during haemodialysis (Article)

2002-01-01T00:00:00Z

BACKGROUND: Intradialytic morbid events such as hypotension and cramps during haemodialysis are generally treated by infusion of iso- or hypertonic solutions. However, differences may exist between solutions with respect to plasma refilling and vascular reactivity. METHODS: We compared the effect of no infusion (NI) with isovolumetric infusion of isotonic saline 0.9% (IS), saline 3% (HS), isotonic glucose 5% (IG), glucose 20% (HG) and mannitol 20% (HM), in six patients during the first hour of six standardized haemodialysis sessions with ultrafiltration. Relative blood volume was monitored continuously by measurement of the intravascular amount of protein. Blood pressure was measured by an oscillometric method, while cardiac output was measured by a thoracic impedance technique. RESULTS: At baseline, no differences in serum urea, sodium, potassium, glucose and osmolarity were found between the various infusion experiments. The maximum increase in relative blood volume directly after infusion was significantly greater with HG (5.1+/-0.7%) than with all other infusions (P<0.05). Stroke volume increased (21.0+/-19.2%, P<0.05) and total peripheral resistance decreased significantly (15.4+/-16.4%, P<0.05) after HG infusions. CONCLUSIONS: Infusion of hypertonic glucose during dialysis results in a greater increase in relative blood volume (RBV) than equal volumes of other solutions. As mannitol has the same osmolarity, molecule mass and charge, the greater increase in RBV following hypertonic glucose appears to be a specific effect, possibly related to a decline in vascular tone. It is therefore uncertain whether the observed increase in plasma volume during hypertonic glucose infusions will be of clinical benefit.

Quantitative flow cytometry shows activation of the TNF-alpha system but not of the IL-2 system at the single cell level in renal replacement therapy (Article)

2001-01-01T00:00:00Z

BACKGROUND: Immunological dysfunction in patients on haemodialysis may be related to imbalanced cytokine systems, such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-2. Despite activation of these systems, haemodialysis patients show high susceptibility for infections and malignancies, and have a poor immunological reaction to T-cell-dependent antigens, like hepatitis B vaccination. In this study we have determined the activation status of the two different cytokine systems, at the single cell level, using quantitative flow cytometry. METHODS: Using fluorescein isothiocyanate- or phycoerythrin-conjugated antibodies directed against TNF-R2 (CD120b), IL-2Ralpha (CD25) and IL-2Rbeta (CD122), we measured the expression of these receptors at the single cell level in order to determine the level of activation of monocytes and T-lymphocytes. RESULTS: Significantly higher expression of the TNF-alpha receptor, TNF-R2, was present on both monocytes and T-lymphocytes in patients on renal replacement therapy (RRT) compared with pre-dialysis chronic renal failure (CRF) patients and controls, indicating activation of the TNF-alpha system. In contrast, IL-2R expression was comparable in all groups studied, which may reflect a non-activated state of the IL-2 system. CONCLUSIONS: The present study illustrates an activated state of the TNF-alpha system in patients on RRT, at the single cell level, while the IL-2 system seems to be unaffected. These findings support the hypothesis that the interaction between the TNF-alpha and IL-2 cytokine systems is disturbed.

Variability of relative blood volume during haemodialysis (Article)

2000-01-01T00:00:00Z

BACKGROUND: A decrease in blood volume is thought to play a role in dialysis-related hypotension. Changes in relative blood volume (RBV) can be assessed by means of continuous haematocrit measurement. We studied the variability of RBV changes, and the relation between RBV and ultrafiltration volume (UV), blood pressure, heart rate, and inferior caval vein (ICV) diameter. METHODS: In 10 patients on chronic haemodialysis, RBV measurement was performed during a total of one hundred 4-h haemodialysis sessions. Blood pressure and heart rate were measured at 5-min intervals. ICV diameter was assessed at the start and at the end of dialysis using ultrasonography. RESULTS: The changes in RBV showed considerable inter-individual variability. The average change in RBV ranged from -0.5 to -8.2% at 60 min and from -3.7 to -14.5% at 240 min (coefficient of variation (CV) 0.66 and 0.35 respectively). Intra-individual variability was also high (CV at 60 min 0.93; CV at 240 min 0.33). Inter-individual as well as intra-individual variability showed only minor improvement when RBV was corrected for UV. We found a significant correlation between RBV and UV at 60 (r= -0.69; P<0.001) and at 240 min (r= -0.63; P<0.001). There was a significant correlation between RBV and heart rate (r= -0.39; P<0.001), but not between RBV or UV and blood pressure. The level of RBV reduction at which hypotension occurred was also highly variable. ICV diameter decreased from 10.3+/-1.7 mm/m(2) to 7.3+/-1. 5 mm/m(2). There was only a slight, although significant, correlation between ICV diameter and RBV (r= -0.23; P<0.05). The change in ICV-diameter showed a wide variation. CONCLUSIONS: RBV changes during haemodialysis showed a considerable intra- and inter-individual variability that could not be explained by differences in UV. No correlation was observed between UV or changes in RBV and either blood pressure or the incidence of hypotension. Heart rate, however, was significantly correlated with RBV. Moreover, IVC diameter was only poorly correlated with RBV, suggesting a redistribution of blood towards the central venous compartment. These data indicate that RBV monitoring is of limited use in the prevention of dialysis-related hypotension, and that the critical level of reduction in RBV at which hypotension occurs depends on cardiovascular defence mechanisms such as sympathetic drive.

Renal insufficiency after heart transplantation: a case-control study (Article)

1998-01-01T00:00:00Z

BACKGROUND: In Rotterdam 304 heart transplants have been performed since 1984. End-stage renal failure, necessitating renal replacement therapy, has developed in 24 patients (8%) after an interval of 25-121 months (median 79 months). After starting renal replacement therapy one-year survival was only 60%. Overall survival after heart transplantation, however, was favourable: 5 and 10 year survival rates of 79% and 50% respectively. METHODS: A case-control study was performed to identify possible risk factors in cases who went on to develop end-stage renal failure compared to controls. RESULTS: We found that renal failure was not limited to elderly patients with ischaemic heart disease, but also occurred in young patients having dilated cardiomyopathy. A significant rise in the serum creatinine was found in cases compared to controls as early as 3 months after transplantation. Cyclosporin dose and trough levels were not different between cases and controls. Neither were there differences in the use of calcium-antagonists or other antihypertensive drugs, allopurinol or diuretics. Rejection incidence was also similar between the two groups. CONCLUSIONS: Renal failure after heart transplantation is a long term complication of cyclosporin use that is not limited to elderly patients with ischaemic heart disease. Cyclosporin dose and trough levels in the cases were not different from patients maintaining stable good renal function, indicating that cyclosporin nephrotoxicity is the result of an individually determined susceptibility to cyclosporin. Suggestions for future strategies to prevent renal failure are given.

Pharmacological manipulation of glomerular barrier function (Doctoral Thesis)

1995-05-24T00:00:00Z

The formation of urine is the result of two opposing processes. A highly dilute pro-urine is produced by ultrafiltration across glomerular capillaries. Extensive reabsorption in the tubules reduces the 180 litres of plasma that are filtered daily to approximately 2 litres of urine which are excreted under normal conditions. The driving force of this massive filtration is a net pressure gradient (hydrostatic pressure difference minus the oncotic pressure of plasma) of only 10 mmHg. The glomerular filtration barrier has the remarkable ability to allow the passage of these vast amounts of fluid while almost totally excluding proteins from the urinary compartment, despite the high concentration of macromolecules in human plasma. The glomerulus therefore acts as a very efficient sieve. The glomerular capillary wall consists of several layers with varying contributions to the sieving characteristics of the kidney.