Reduced clearance of rocuronium and sugammadex in patients with severe to end-stage renal failure: a pharmacokinetic study.

BACKGROUND: Sugammadex is a selective relaxant binding agent designed to encapsulate the neuromuscular blocking agent, rocuronium. The sugammadex-rocuronium complex is eliminated by the kidneys. This trial investigated the pharmacokinetics (PKs) of sugammadex and rocuronium in patients with renal failure and healthy controls. METHODS: Fifteen ASA class II-III renal patients [creatinine clearance (CL(CR)) <30 ml min(-1)] and 15 ASA I-II controls (CL(CR) > or =80 ml min(-1)) were included. After induction of anaesthesia, a single i.v. dose of rocuronium 0.6 mg kg(-1) was given, followed by a single i.v. dose of sugammadex 2.0 mg kg(-1) at reappearance of the second twitch of the train-of-four response. Plasma concentrations of rocuronium and sugammadex were estimated and PK variables determined using non-compartmental analyses. Percentages of sugammadex and rocuronium excreted in the urine were measured. RESULTS: PK data were obtained from 26 patients. Mean total plasma clearance (CL) of sugammadex was 5.5 ml min(-1) in renal patients and 95.2 ml min(-1) in controls (P<0.05). Rocuronium CL was 41.8 ml min(-1) in renal patients and 167 ml min(-1) in controls (P<0.05). The median amount of sugammadex and rocuronium excreted in the urine over 72 h in renal patients was 29% and 4%, respectively, and 73% and 42% over 24 h in controls. CONCLUSIONS: Large differences in the PKs of sugammadex and rocuronium between patients with renal failure and healthy controls were observed. The effect of renal impairment on the PK variables of rocuronium was less than with sugammadex. Urinary excretion of both drugs was reduced in renal patients.

Placental disposition of the immunosuppressive drug tacrolimus in renal transplant recipients and in ex vivo perfused placental tissue.

Currently, tacrolimus is the most potent immunosuppressive agent for renal transplant recipients and is commonly prescribed during pregnancy. As data on placental exposure and transfer are limited, we studied tacrolimus placental handling in samples obtained from renal transplant recipients. We found transfer to venous umbilical cord blood, but particularly noted a strong placental accumulation. In patient samples, tissue concentrations in a range of 55-82 ng/g were found. More detailed ex vivo dual-side perfusions of term placentas from healthy women revealed a tissue-to-maternal perfusate concentration ratio of 113 ±â€¯49 (mean ±â€¯SEM), underlining the placental accumulation found in vivo. During the 3 h ex vivo perfusion interval no placental transfer to the fetal circulation was observed. In addition, we found a non-homogeneous distribution of tacrolimus across the perfused cotyledons. In conclusion, we observed extensive accumulation of tacrolimus in placental tissue. This warrants further studies into potential effects on placental function and immune cells of the placenta.

[A genetic childhood disease with consequences in adult life: the Denys-Drash syndrome]. / Een genetische kinderziekte met gevolgen op de volwassen leeftijd: Denys-Drash-syndroom.

In a 17-year-old woman with absent sexual development and a congenital nephrotic syndrome leading to renal failure, the Denys-Drash syndrome was diagnosed after development of an ovarian dysgerminoma. The Denys-Drash syndrome is characterised by the triad: progressive nephropathy due to diffuse mesangial sclerosis, male pseudo-hermaphroditism (XY karyotype with ambiguous or female genital organs) and an increased risk of developing Wilms' tumour and gonadoblastoma. The syndrome is generally caused by a genetic defect in the Wilms' tumour suppressor 1 gene (WT1 gene). A WT1 mutation and XY karyotype were also found in this patient. The WT1 gene encodes a transcription factor playing an important role in renal and genital development. The diagnosis of Denys-Drash syndrome had important consequences for the follow-up and treatment of the patient. The second gonad and the native kidneys were removed due to the increased risk of malignancy. Moreover, the finding of a XY karyotype could result in serious psychic problems. Physicians responsible for the health of adults are confronted more and more often with the consequences of childhood diseases. This case illustrates the necessity to inform such physicians about previously untreatable genetic diseases of childhood so that the adequate medical management of these patients can be guaranteed.

Metoclopramide stimulates kaliuresis during felodipine without affecting its natriuresis.

Calcium entry blockers such as felodipine induce natriuresis without a parallel rise of potassium excretion. Previous studies with exogenous aldosterone and felodipine have suggested that the absence of kaliuresis might be explained by a felodipine-induced inhibition of aldosterone release. The natriuresis with calcium entry blockers could not be attributed to a similar mechanism but might be due to the stimulation of intrarenal natriuretic systems such as the dopaminergic system. We studied whether the aselective dopamine antagonist metoclopramide prevents the natriuresis with low and therapeutic felodipine doses and whether metoclopramide-induced aldosterone release promotes kaliuresis with felodipine. Twelve healthy male volunteers participated in a randomized, placebo-controlled, crossover study comparing felodipine infusion during metoclopramide with felodipine alone. Metoclopramide had no significant influence on the pronounced and dose-dependent increases of renal plasma flow and urinary sodium excretion with felodipine. Metoclopramide increased plasma aldosterone concentration from 0.17 +/- 0.03 to 0.60 +/- 0.14 nmol/L, and subsequent felodipine infusion clearly increased urinary potassium excretion by 23 +/- 6 and 35 +/- 8 mumol/min (low and therapeutic doses, respectively). In contrast, potassium excretion remained stable with felodipine alone (+5 +/- 4 and +7 +/- 5 mumol/min, respectively). In conclusion, the natriuretic action of calcium entry blockers cannot be blocked by the aselective dopamine antagonist metoclopramide. This natriuresis is accompanied by kaliuresis only in the presence of elevated endogenous aldosterone concentrations. The ability of calcium entry blockers to prevent a rise of plasma aldosterone thus seems essential for the prevention of urinary potassium losses.

Oedema formation with the vasodilators nifedipine and diazoxide: direct local effect or sodium retention?

OBJECTIVE: To determine whether the common side effect of ankle oedema with arteriolar vasodilators such as the calcium entry blocker (CEB) nifedipine and the potassium channel opener (PCO) diazoxide is the direct result of peripheral vasodilation or merely a consequence of renal sodium retention. DESIGN: In 12 healthy sitting volunteers we studied for 3 h the effects of 20 mg nifedipine, 150 mg diazoxide intravenously, 25 mg captopril and placebo on oedema formation and sodium excretion. CONCLUSIONS: Foot swelling was determined with a new accurate device (coefficient of variation 0.30%), which uses Archimedes principle to measure water displacement induced by immersion of the foot. Blood pressures were recorded with a Hawksley random-zero sphygmomanometer. RESULTS: All of the active drugs decreased diastolic blood pressure (captopril by 9 +/- 2%, nifedipine by 4 +/- 3% and diazoxide by 2 +/- 2%, compared with an increase of 5 +/- 2% with placebo). Foot volume increased acutely after administration of nifedipine (by 2.6 +/- 0.4%), whereas it remained stable with placebo and the other drugs. Administration of captopril and nifedipine induced increases of fractional sodium excretion (by 20 +/- 9% and 40 +/- 20%, respectively) in contrast to the decreases with placebo and diazoxide (by 13 +/- 11% and 24 +/- 10%, respectively). Only administration of nifedipine induced significant, albeit small, increases in haemoglobin and serum albumin levels. CONCLUSIONS: Administration of nifedipine increased foot volume and natriuresis simultaneously, thereby supporting the hypothesis that development of ankle oedema with CEB is a local phenomenon at the site of vasodilation. The absence of a similar increase in foot volume with diazoxide administration should be interpreted with caution because of the rather minor effect of this dose of diazoxide on blood pressure. However, it could be indicative of a different mechanism of oedema formation with PCO.

Comparing outcomes in renal replacement therapy: how should we correct for case mix?

The need to evaluate the effectiveness of clinical practice to justify expensive therapy in the face of financial constraints in all areas of health care delivery makes it necessary to identify groups of patients who are likely to benefit most from treatment. Various risk stratification methods have been used for analyzing survival probabilities for patients receiving renal replacement therapy. Complicated risk stratification methods produce large numbers of risk groups of small sizes, which makes comparison between individual centers difficult. We compared three simple methods of risk stratification, that divided patients into low-, medium-, and high-risk groups, in a cohort of 1,407 patients who commenced renal replacement therapy in five European countries during a 7-year period. Method 1 considered age (>55 years) and diabetes alone; method 2 used a higher age limit (>70 years) and comorbid illnesses, including those other than diabetes; and method 3 used only the number of comorbidities (none, 1, or > or =2) for stratification. Kaplan-Meier survival curves were constructed for comparison between risk groups and Cox's regression model used to assess strength of relationship with mortality. Although patient survival was significantly different between the low-, medium-, and high-risk groups using all three methods, Cox's regression analysis showed that method 2 provided the greatest discrimination between risk groups. In predicting mortality, method 2 (based on comorbidities and age) showed the highest sensitivity and specificity (84% and 80%, respectively) compared with method 1 (80% and 74%) and method 3 (64% and 82%). Validation of this approach in other populations in a prospective study is required before this method, which takes into account the influences of both age and comorbidity for risk stratification, can be used for comparing survival data and for presenting results of renal replacement therapy.

Acute renal effects of felodipine in hypertensive patients with kidney disease.

In contrast to other types of directly acting vasodilators, calcium antagonists promote sodium excretion. It is not well established, however, whether these drugs also induce natriuresis in hypertensive patients with renal disease. Therefore, we studied the acute effects of the dihydropyridine calcium antagonist felodipine in nine such patients (CCr 68 +/- 19 ml/min) and 12 healthy normotensive subjects. In both the hypertensive patients and the normotensive subjects total and fractional sodium excretion rose during the first 40 minutes of intravenous felodipine infusion; in the hypertensive patients this rise of sodium excretion was positively correlated to the initial glomerular filtration rate (GFR) (r = 0.87, P less than 0.01). In the patients, during ongoing felodipine infusion, natriuresis was attenuated in the setting of a large continuing decrease of blood pressure. In contrast, in the normotensive subjects, in whom blood pressure did not fall any further, a steady rise of sodium excretion was observed. In both the hypertensive patients and the normotensive subjects GFR remained unchanged and renal vascular resistance decreased, whereas renal plasma flow increased only in the latter group. Changes in sodium excretion were not correlated to changes in renal hemodynamic parameters. It is concluded, that also in hypertensive patients with diminished renal function felodipine exerts a potentially advantageous natriuretic effect. However, this natriuretic effect is possibly less at lower GFR and seems to be attenuated by blood pressure reduction. The mechanism of this natriuretic effect as well as its contribution to the antihypertensive effect of felodipine still has to be clarified.

Is natriuresis on felodipine due to reversal of the renal effects of angiotensin II?

Felodipine induces natriuresis, possibly by renal hemodynamic and/or tubular effects. Theoretically, reversal of the sodium-retaining effect of angiotensin II (Ang II) could be involved. Therefore, we administered felodipine during Ang II infusion and during suppression of endogenous Ang II production in two double-blind studies in healthy volunteers. First, a gradually increasing dose of Ang II was infused during felodipine or solvent infusion. Before starting Ang II, felodipine had lowered renal vascular resistance (RVR) and filtration fraction (FF), and simultaneously increased CNa. The Ang II induced rise of mean arterial pressure (MAP) and renal vasoconstriction was partly antagonized and the falls in glomerular filtration rate (GFR) and CNa completely abolished by felodipine. The combination of felodipine and 3.0 ng/kg/min Ang II even enhanced natriuresis. Second, felodipine or solvent was infused after one week of pretreatment with placebo or the angiotensin converting enzyme (ACE) inhibitor ramipril, which reduced MAP and induced renal vasodilatation. Ramipril pretreatment did not influence significantly the blood pressure reduction, renal vasodilatation, and natriuresis caused by felodipine. In conclusion, it seems unlikely that the natriuretic effect of felodipine is due to interference with renal effects of endogenous Ang II. The fact that felodipine reverses sodium retention on exogenous Ang II may be explained by interference with systemic and renal hemodynamic effects of exogenous Ang II.

Two cases of subcutaneous Scedosporium apiospermum infection treated with voriconazole.

Scedosporium apiospermum is a mold that is increasingly being recognized as an opportunistic pathogen in immunocompromised patients, and treatment is complicated by intrinsic resistance to several antifungal agents. In our hospital, two cases of S. apiospermum infection occurring within 2 weeks were successfully treated with voriconazole. Since both patients were infected with an uncommon pathogen, a search for a common nosocomial source was performed. As environmental cultures yielded no S. apiospermum, and random amplified polymorphic DNA (RAPD) fingerprinting showed that the patients' strains were genotypically unrelated, we considered a common nosocomial source of S. apiospermum to be unlikely.

The immunofluorometric TSH assay as first-line test for suspected thyroid dysfunction.

In this study of 103 patients with suspected thyroid dysfunction, the diagnostic value of a single basal immunofluorometric (IFMA) TSH measurement was evaluated and compared with the classical TRH test with RIA-TSH measurements, plasma TT4 concentrations and FT4I. A single basal TSH determination accurately predicted the TRH-stimulated TSH response, making the TRH test redundant in most patients. Because undetectable basal TSH did not always exclude a small rise in TSH, the TRH test could still be indicated in patients receiving thyroxine suppression therapy for thyroid cancer. Basal TSH differentiated accurately between euthyroidism and thyroid dysfunction, especially at the decision values of 0.20 and 4.0 mU/l, as proposed in this study. For diagnosis of clinical and subclinical hypo- and hyperthyroidism, additional measurement of TT4 and/or FT4I is necessary. A 2-yr follow-up of patients with subclinical thyroid dysfunction did not show progression to clinical disease. In some of the patients with subclinical hypothyroidism, substitution therapy with thyroxine had been started after initial testing. Indications for treatment of subclinical thyroid dysfunction are discussed.

Living kidney transplantation in adult patients with atypical haemolytic uraemic syndrome.

BACKGROUND: Dysregulation of complement activation is the most common cause of the atypical haemolytic uraemic syndrome (aHUS). Many patients with aHUS develop end-stage renal disease and consider kidney transplantation. However, the recurrence rate after transplantation ranges from 45-90% in patients with known abnormalities in circulating complement proteins. It was recently proposed that patients with aHUS should be treated prophylactically with plasma exchange or eculizumab to prevent recurrence after transplantation. METHODS: A case series describing the successful outcome of kidney transplantation without prophylactic therapy in four adult patients with aHUS and a high risk of disease recurrence. Patients received a living donor kidney and immunosuppression consisting of basiliximab induction, low-dose tacrolimus, prednisone and mycophenolate mofetil. Patients received a statin, and were targeted to a low blood pressure preferably using blockers of the renin-angiotensin system. RESULTS: After a follow-up of 16-21 months, none of the patients developed recurrent aHUS. Also, no rejection was observed. CONCLUSIONS: Kidney transplantation in adult patients with aHUS can be successful without prophylactic eculizumab, using a protocol that minimises cold ischaemia time, reduces the risk of rejection and provides endothelial protection. Our data suggest that in patients with aHUS, controlled trials are needed to demonstrate the optimal strategy.

Infection control of hepatitis C in Dutch dialysis centres.

BACKGROUND: In dialysis patients, blood transfusions and long-term dialysis are well-known risk factors for transmission of hepatitis C virus (HCV). Transmission of HCV by transfusions has become extremely rare since the introduction of antibody screening. However, nosocomial transmission of HCV within dialysis units still occurs. We performed a survey of current infection control measures against HCV in Dutch dialysis centres that had participated in a national HCV prevalence study. METHODS: All twenty-seven Dutch dialysis centres where HCV-positive patients had been identified (HCV prevalence 1-8%), participated. With the use of a questionnaire we evaluated screening procedures for resident patients and guest patients, routine hygienic measures in HCV-positive and -negative patients, and cleaning procedures of dialysis equipment. RESULTS: All centres except one screened new patients for HCV antibodies, but the frequency of periodic follow-up screening varied. Most centres requested HCV antibody screening of guest patients in advance, but in daily practice 55% of the centres dialysed guest patients even when HCV antibody status was not available. The majority of centres had not implemented special precautions for patients with unknown HCV antibody status. In most centres the use of protective glasses, masks and aprons depended on the HCV antibody status of the patients. Surprisingly, 85% of the centres allowed their nurses to operate dialysis machines with gloves possibly blood contaminated. All centres sterilized their machines at the end of the day, but only 77% sterilized their machines between all dialysis sessions. Traces of blood were removed with alcohol in 63% of the centres. CONCLUSION: Dutch dialysis centres have not yet implemented an optimal policy for prevention of HCV. Especially, operating dialysis machines with gloves might be a potential source for nosocomial transmission of HCV, not yet covered by the issued guidelines. Because dialysis patients probably have a prolonged serological window phase after a recent HCV infection, it does not suffice to implement a preventive strategy against nosocomial transmission based on the results of HCV antibody screening. Universal, rigorous implementation of adequate infection control measures irrespective of HCV antibody status should be the cornerstone for prevention of nosocomial transmission of HCV and other blood borne pathogens.

Angiotensin-converting enzyme inhibition and the combination of a beta blocker and a diuretic are equally effective in lowering proteinuria in patients with glomerulonephritis.

In this study we compared the antihypertensive and antiproteinuric efficacies of an angiotensin-converting enzyme inhibitor and of conventional treatment consisting of a beta blocker and a diuretic in 13 patients with biopsy-proven glomerulonephritis and a proteinuria of more than 2 g/24 h. Ten of these 13 patients were normotensive. None had diabetes mellitus. In a randomized cross-over design with two treatment periods of 6 weeks, each preceded by a washout period of 4 weeks, patients were treated with benazepril (20 mg o.d.) and the combination of metoprolol (200 mg o.d.) and chlorthalidone (25 mg o.d.). At the end of the treatment periods with benazepril or metoprolol/chlorthalidone mean arterial pressure was lowered to a similar degree by 7.4 (mean, 95% confidence interval 2.0-12.7) and 9.7 (5.7-13.7) mmHg respectively. Both treatment modalities caused similar reductions in proteinuria, being 3.4 g/24 h (mean, 95% confidence interval 2.1-4.8) on benazepril and 3.2 (1.2-5.1) g/24 h on metoprolol/chlorthalidone. Glomerular filtration rate and renal plasma flow were slightly less during metoprolol/chlorthalidone treatment. Subgroup analysis of normotensive patients gave similar results. In conclusion, in these patients with glomerular disease angiotensin-converting enzyme inhibition was not more effective than the conventional treatment with the combination of a beta blocker and a diuretic in reducing blood pressure and proteinuria. Both treatments reduced proteinuria not only in hypertensive, but also in normotensive patients.

Exogenous aldosterone antagonizes distal tubular effects of calcium entry blocker felodipine.

Calcium entry blockers, such as felodipine, increase natriuresis without increasing kaliuresis. Since these drugs acutely increase plasma renin activity without a concomitant change of aldosterone, inhibition of such stimulated aldosterone release might explain the absence of kaliuresis. In a randomized crossover study in 12 male volunteers, we compared the effects of simultaneously administered exogenous aldosterone and felodipine with the effects of either felodipine or aldosterone alone. Felodipine infusion decreased blood pressure, increased renal plasma flow, and induced natriuresis without kaliuresis. Aldosterone alone reduced sodium excretion and increased potassium excretion without influencing hemodynamics. Addition of aldosterone to felodipine attenuated its natriuretic effect and induced a kaliuresis, which clearly exceeded the rise of potassium excretion during aldosterone alone [delta% fractional excretion of K+ +42 +/- 12 with felodipine+aldosterone and +7 +/- 8% with aldosterone alone; means +/- SE, P < 0.02]. Our data suggest that felodipine-mediated inhibition of stimulated aldosterone release is essential for the absence of kaliuresis with felodipine. In addition, the pronounced kaliuresis with aldosterone during felodipine is in keeping with increased distal sodium delivery due to a proximal tubular action of felodipine.

Renal and systemic effects of atenolol and tertatolol in renal transplant recipients on cyclosporine A.

BACKGROUND: Hypertension and nephrotoxicity are well-known side-effects of cyclosporine A (CsA). CsA-induced vasoconstriction of the afferent glomerular arteriole probably plays a role in at least the nephrotoxicity. Frequently renal transplant recipients on CsA have to be treated with antihypertensive drugs and for this purpose also beta-blockers are used. Tertatolol is a new beta-blocker with specific vasodilatory properties, and thus might be particularly useful in CsA-treated transplant recipients. METHODS: We studied the systemic and renal haemodynamic effects of atenolol and tertatolol in 12 hypertensive renal transplant recipients on cyclosporine A (CsA). In a cross-over way, all patients were treated with atenolol and tertatolol for 4 weeks each, separated by a wash-out period also of 4 weeks. At the end of each period, the mean arterial pressure (MAP), heart rate, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured. RESULTS: The mean arterial pressure was lower (P < 0.05) during atenolol (124 +/- 2 mm Hg) and tertatolol (125 +/- 2 mm Hg) treatment compared with washout (132 +/- 4 mm Hg). Also the heart rate was lower (P < 0.01) during atenolol and tertatolol (54 +/- 3 and 55 +/- 2 beats/min respectively) than in the wash-out period (65 +/- 3 beats/min). GFR and RPF were not changed by either beta-blocker. CONCLUSION: In CsA treated renal transplant recipients both atenolol and tertatolol effectively reduced blood pressure. In these patients we found no evidence of a specific vasodilatory effect of tertatolol. Both beta-blockers had no negative influence on renal function. Hence, these cardioprotective agents are an attractive and safe choice for the treatment of hypertension in such patients.

Angiotensin converting enzyme inhibition does not prevent the natriuretic effect of felodipine.

The mechanism of natriuresis with calcium entry blockers such as felodipine is largely unexplained. As these drugs prevent sodium retention following exogenous angiotensin II, the natriuretic effect of felodipine might be due to a similar interaction with endogenous angiotensin II. In such a case, angiotensin converting enzyme inhibition with ramipril should prevent natriuresis with felodipine. We tested this hypothesis in a randomized, double-blind, crossover study in 12 male volunteers by comparing intravenous felodipine after 1 week of oral ramipril with felodipine after placebo and with solvent after ramipril. Ramipril pretreatment reduced ACE activity to 11 +/- 1%, lowered the blood pressure, and increased renal blood flow. However, ramipril pretreatment did not prevent the pronounced increase in natriuresis and diuresis with felodipine. Fractional sodium excretion only tended to increase less during felodipine after ramipril than during felodipine after placebo (absolute changes of + 1.2 +/- 0.2 and + 1.7 +/- 0.2%, respectively; p = 0.07). Ramipril did not influence the felodipine-mediated blood pressure reduction and renal vasodilation. In conclusion, ACE inhibition has no significant effect on the natriuretic and hemodynamic effects of felodipine, suggesting that mechanisms other than interaction with endogenous angiotensin II are involved in these effects of calcium entry blockers.

Acute effects of nifedipine in renal transplant recipients treated with cyclosporine or azathioprine.

Cyclosporine (CsA) impairs renal function, probably by preglomerular vasoconstriction. Vasodilating substances may therefore be of benefit to ameliorate CsA-induced renal dysfunction. We studied the acute effects on blood pressure and renal function of the dihydropyridine calcium antagonist nifedipine (10 mg orally) in 20 CsA-treated renal transplant patients. In addition, we compared the effects of nifedipine when given immediately before and 4 weeks after elective conversion from CsA to azathioprine. Compared with placebo (n = 14), administration of nifedipine led to a significant decrease in blood pressure and a strong natriuretic and diuretic response. Despite the reduction in blood pressure, glomerular filtration rate improved from 60 +/- 20 (mean +/- SD) to 69 +/- 24 mL/min/1.73 m2 (P < 0.001) and renal plasma flow (RPF) increased from 260 +/- 87 to 338 +/- 120 mL/min/1.73 m2 (P < 0.001). The combination of a decreased blood pressure with an increased RPF was reflected in a sharp decrease in renal vascular resistance (0.34 +/- 0.18 units v 0.23 +/- 0.10 units; P < 0.001). The conversion from CsA to azathioprine by itself led to significant increases in glomerular filtration rate (62 +/- 15 mL/min/1.73 m2 v 76 +/- 18 mL/min/1.73 m2; P < 0.05) and RPF (280 +/- 86 mL/min/1.73 m2 v 334 +/- 66 mL/min/1.73 m2; P < 0.05). During treatment with azathioprine an effect of nifedipine on glomerular filtration rate and RPF was no longer observed, although the natriuretic effect was similar on both occasions. The decrease in renal vascular resistance was larger during treatment with CsA than during treatment with azathioprine (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating concentrations of soluble interleukin 6 receptors gp80 and gp130 in chronic renal failure and effects of renal replacement therapy.

BACKGROUND: Circulating receptors modulate the biological effects of cytokines. Renal insufficiency is known to influence the concentrations of the soluble tumor necrosis factor (TNF) receptors p55 and p75. No data are available on the concentrations of the circulating interleukin 6 (IL-6) receptors gp80 and gp130 during chronic renal insufficiency. METHODS: We compared the serum concentrations of the IL-6 receptors gp80 and gp130 to those of the TNF receptors p55 and p75 in end-stage chronic renal failure, continuous ambulatory peritoneal dialysis, and hemodialysis (HD). RESULTS: In healthy controls the concentrations of gp80, gp130, p55, and p75 in serum were 82.1 +/- 24.3, 87.9 +/- 20.2, 1.1 +/- 0.2, and 1.7 +/- 0.3 ng/ml, respectively. These concentrations were increased to, respectively, 112.2 +/- 18.0, 186.0 +/- 37.7, 10.5 +/- 4.3, and 15.0 +/- 7.5 ng/ml in chronic renal failure, to 138.8 +/- 18.0, 181. 3 +/- 46.1, 25.5 +/- 5.2, and 19.1 +/- 3.4 ng/ml in continuous ambulatory peritoneal dialysis, and to 107.9 +/- 29.4, 146.6 +/- 30. 5, 22.9 +/- 6.3, and 16.8 +/- 6.0 ng/ ml in HD (before dialysis session). The concentrations after HD were higher for p75 only. CONCLUSIONS: The data show that the concentrations of the IL-6 receptors (gp80 and gp130) are elevated in chronic renal insufficiency. The increase is relatively low as compared with the elevation of the TNF receptors in this situation. HD does not result in a consistent change in serum concentrations of the various receptors.