Lung function in adult patients with cystic fibrosis after using the eFlow rapid for one year.

BACKGROUND: The new generation nebuliser PARI eFlow® rapid allows a highly efficient aerosol delivery at reduced inhalation time. However, lung function data during long-term use of this device are not available until now. METHODS: 70 clinically stable adult cystic fibrosis patients participated in this observation study. Lung function tests were performed prospectively 12 weeks after and again 9 to 12 months after switching the inhalation device from a conventional jet nebulizer to the PARI eFlow® rapid. Lung function data were collected retrospectively from the visits 1 year as well as 12 weeks prior to the switch-over. Lung function data for all time points were only available for 59 patients. Treatment time and patient's satification were recorded for both conventional and new nebuliser in all 70 patients. RESULTS: After 1 year of inhalation with eFlow® rapid, the mean change in FEV1% was - 1.4% (n = 59 patients). The decrease in FEV1 was smaller than the change in FEV1 after 1 year of inhalation with the conventional jet nebuliser (control period, -3.1%), although this difference was not statistically significant. The same effect was seen in MEF25(%) (-2.6% with conventional nebuliser compared to -1.6% after eFlow® rapid). Concerning the FVC, there was a greater improvement after 1 year of inhalation with the eFlow® rapid than with the jet nebuliser (+ 2.9% vs. +1.1%). For PEF%, there was an increase during the control period, whereas after inhalation with eFlow® rapid there was a decrease (+1.1% vs. -2.9%). All changes were not significantly different. The eFlow® rapid reduced total daily inhalation time by two-thirds (conventional nebuliser: 31.1 min/day; eFlow® rapid: 10.2 min/day, n = 70 patients). CONCLUSION: Inhalation with the new nebuliser eFlow rapid does not alter FEV1, FVC or PEF significantly after 1 year of inhalation. The treatment time could be reduced significantly by the eFlow® rapid.

Adherence to prescribed oral medication in adult patients undergoing chronic hemodialysis: a critical review of the literature.

OBJECTIVE: Poor adherence to complex multimodal therapies is a widely recognized problem in the daily care of dialysis patients, contributing to excess morbidity and mortality of this population. While a few studies have been devoted to understanding patient nonadherence, their results were somewhat controversial. The goals of this review are to quantify nonadherence to certain oral medications, to raise awareness of factors that may cause problems in a patient;s adherence to this treatment, and to describe strategies that may be used to improve adherence to prescribed pharmacotherapy. METHODS: A systematic literature review in the MEDLINE and PubMed database (1971-2008) was performed. Quantitative studies, which accurately indicated the total percentages of nonadherence to oral medication in adult patients receiving chronic hemodialysis, were identified. RESULTS: A total of 19 studies fulfilled the search criteria. Rates of nonadherence to the oral medication ranged from 3 - 80%. More than half of the included studies reported nonadherence rates of > or = 50% (mean 67%). The use of phosphate binding therapy was the prevalent surveyed oral medication. Self reports, structured interviews, and predialysis serum phosphate levels were the most frequent assessment tools used to record adherence rates. Limitations of the reviewed studies included small patient cohorts, inconsistent definitions of adherence, and a lack of standardized methods for measuring nonadherence. CONCLUSIONS: Nonadherence to oral medication in hemodialysis patients is still an underestimated, but life-threatening behaviour.

Acute kidney injury as a risk and progression factor for chronic kidney injury.

Acute kidney injury is common in hospitalized patients and is associated with significant in-hospital morbidity and mortality. However, hospital-acquired acute kidney injury is neither a harmless complication of severe underlying diseases nor a life threatening short-term illness. Posthospital discharge follow-up of patients highlights that survivors of acute kidney injury may develop serious long-term sequelae. Long-term mortality is greater in those patients who survived acute kidney injury when compared with critically or non-critically ill patients without acute kidney injury. Among survivors of acute kidney injury at long-term follow-up approximately 12.5% may be dialysis dependent and 19-31% may have chronic kidney disease. The incidence of end-stage renal disease secondary to acute kidney injury will likely continue to increase with more elderly patients treated in Intensive Care Units, with a higher burden of extra renal and renal comorbid diseases. Nephrologists should recognize acute kidney injury as an underestimated cause of chronic kidney disease and patients who survive with incomplete recovery should be followed closely for new chronic kidney disease or progression of pre-existing chronic kidney disease. Non-recovery or re-need for dialysis are not only important determinants of long-term health status, quality of life and mortality of these patients, but add also a burden to health resources.

Two consecutive episodes of acute hepatitis C with different genotypes in a hemodialysis patient responsive to PEG-interferon monotherapy.

We report the case of a 63-year-old male patient on long-term hemodialysis who suffered two consecutive episodes of persistent hepatitis C virus infection with different genotypes and was successfully treated with pegylated IFN-alpha monotherapy each time.

Renal recovery after severe acute renal injury.

BACKGROUND: Recovery of renal function after acute renal injury is an important clinical determinant of patient morbidity and mortality. However, studies covering this field are scarce and nonhomogeneous. FINDINGS: Despite success in animal models, translation of current pharmacologic strategies to limit the extent of kidney dysfunction or to hasten renal recovery from acute kidney injury (AKI) in human studies has failed. Renal replacement therapy is the mainstay of supportive care in patients with AKI. However, its performance can have untoward effects that contribute to the prolongation of the course of AKI or impede the ultimate recovery of complete renal function. Use of biocompatible membranes, daily hemodialysis, advanced intermittent hemodialysis (IHD) technology or continuous RRT (CRRT) have been coupled with shortened renal recovery after AKI. Rate of renal recovery to RRT independence is variable when judged at hospital discharge. The frequency of end-stage renal disease in survivors from AKI is highest in severe acute parenchymal renal disease and lowest in acute tubular necrosis (ATN). Renal recovery is less likely in patients with preexisting renal disease. Renal recovery at hospital discharge may underestimate the true rate of renal recovery. The overwhelming majority of patients (more than 85 %) with severe ATN precipitating on normal renal function recover and maintain complete renal function or any degree of chronic renal functional impairment within 6-12 months after AKI. Partial or nonrecovery of renal function represents an independent predictor of long-term mortality for survivors from AKI. Re-need for RRT occurs in a small portion of survivors of severe ATN (less than 5%). CONCLUSION: Severe AKI necessitating RRT should no longer simply be viewed as just an acute reversible complication of critical illness or short-term illness. Persistent reduction in renal function will exhibit independent effects on patient survival that extends well beyond discharge from the hospital.

Lung disease severity, chronic inflammation, iron deficiency, and erythropoietin response in adults with cystic fibrosis.

Chronic lung disorders are usually associated with a hypoxia driven increase in red cell mass. However, patients with cystic fibrosis (CF) often have normal or decreased haemoglobin levels. The present prospective observational study in cystic fibrosis patients was performed to determine which factors were involved in alterations in the hematopoetic response to corresponding arterial oxygen pressure. Sixty adult patients (age 21-51) with stable CF were included. They all had vitamin A, D, E, and K but no vitamin B12 supplementation. Twenty-five patients were on oral Fe(2+) (100 mg/day). Resting arterial blood gases, lung function, complete blood counts, parameters of iron status, CRP, sputum microbiology and serum erythropoietin were measured at recruitment and after 3 and 6 months. Patients had varying degrees of pulmonary functional impairment and 9% were hypoxemic (arterial oxygen pressure <60 mm Hg). Low-grade systemic inflammation (CRP > 0.5 mg/dl) was present in 40% of the patients, who all had bacterial colonization. None of the patient had erythrocytosis and 12 patients had anemia. There was no significant difference in iron status between patients with or without chronic iron supplementation and erythropoietin levels were normal. During the 6 months observation period no significant changes occurred. The patients exhibited an impaired erythropoietic response to hypoxemia with normal or low hematocrit in spite of chronic lung disease which might be caused by chronic inflammation associated with CF. Linear multivariate regression analysis revealed CRP levels but neither iron substitution, nor erythropoietin levels nor lung function parameters as independent determinant of haemoglobin levels. CF may be associated with anemia of variable severity as expression of the chronic inflammation present in these patients. The therapeutic consequences are to treat the underlying inflammation rather than to supplement iron.

Prospective randomized cross-over long-term comparison of online haemodiafiltration and ultrapure high-flux haemodialysis.

BACKGROUND: The residual uraemic syndrome that is inadequately cleared by diffusion is thought to contribute to the poor outcome of maintenance dialysis patients. Haemodiafiltration combines diffusion and convection in a single therapy, conferring theoretical benefits over haemodialysis. However, only few randomised comparisons have been carried out. METHODS: The prospective crossover clinical evaluation of high-flux ultrapure haemodialysis and online haemodiafiltration included 76 clinically stable patients on low-flux conventional bicarbonate buffered haemodialysis. They were randomized to high-flux haemodialysis or online haemodiafiltration (24 months) and switched to the alternative treatment (24 months). RESULTS: Removal of urea (Kt/V) and phosphate was significantly greater for online haemodiafiltration than for haemodialysis. Both high-flux haemodialysis and haemodiafiltration were associated with sustained reductions of pretreatment beta 2 microglobulin levels, however, the decrease was greater with haemodiafiltration. Both modes of renal replacement therapy significantly improved nutritional status and the haematopoietic response to rHu EPO. Under unmatched conditions (sodium and energy balance) haemodiafiltration was associated with a lower number of hypotensive episodes and partial improvement of quality of life. The incidence of death was low in both groups and did not differ among the two modes of renal replacement therapy. CONCLUSION: Online haemodiafiltration is a safe, effective and well tolerated therapy for end-stage renal disease patients even in the long run. Whether the dismal mortality rates of unselected end-stage renal disease patients can be changed by online haemodiafiltration remains to be shown in large scale long-term trials.

Nasal carriage of meticillin resistant Staphylococcus aureus: the prevalence, patients at risk and the effect of elimination on outcomes among outclinic haemodialysis patients.

OBJECTIVE: Haemodialysis (HD) patients with meticillin-resistant Staphylococcus aureus (MRSA) infections face high morbidity and mortality. Nasal carriage of Staphylococcus aureus is known to play an important role as an endogenous source for HD-access-related infections that contribute significantly to morbidity, mortality and cost of end-stage renal disease (ESRD) management. This prospective investigation in regular out-clinic haemodialysis patients was undertaken to estimate the prevalence of S.aureus nasal carriage, to define patient groups at risk and to evaluate the effect of elimination on outcomes among outclinic haemodialysis patients. METHODS: 136 HD patients without signs of overt clinical infection (48 women, 88 men, age 22-88 years) were screened at least twice for the nasal carriage for meticillin-susceptible SA (MSSA) or meticillin-resistant SA (MRSA). Nasal carriage of S. aureus was related to demographic (age, gender, duration on HD), comorbidity (diabetes, malignancy) and exposure to health care (dialysis staff, hospitalisation). Nasal carriers for MRSA received standardized mupirocin therapy and were followed up for elimination and infections for 1 year. RESULTS: The prevalence of nasal carriage for staphylococcus aureus was 53 % (41 % MSSA, 12 % MRSA). Compared with patients showing no colonization or with MSSA carriers, the 16 patients with nasal carriage for MRSA were older and more likely to have acquired the bacteria while hospitalised. Genotyping of MRSA isolates revealed different strains in patients and care-providers. Mupirocin eliminated MRSA in all patients, none of these patients experienced an infection caused by staphylococcus aureus, confirming the known value of MRSA elimination from other studies. CONCLUSIONS: Elderly patients hospitalised for surgery constitute a high risk group for nasal carriage for MRSA. Early diagnosis may help prevent clinically relevant infection. Elimination of colonization by mupirocin appears to be an attractive preventive strategy.

Dosing pattern of renal replacement therapy in acute renal failure: current status and future directions.

Acute renal failure (ARF) is associated with poor clinical outcome, particularly in critically ill patients. Different renal replacement techniques are available for treatment of ARF, but a general consensus of standardization of treatment dose is lacking. Recent prospective investigations in critically ill patients with ARF utilizing either intermittent or continuous renal replacement therapy established a clear dose-outcome relationship. However, several surveys of current practices of renal replacement therapy dosing in acute renal failure revealed, that the majority of ICU patients with ARF received dialysis doses lower than prescribed for stable end-stage renal disease patients. Most nephrologists did not perform formal dose calculation. Future patterns of dosing renal replacement therapy should focus both on an earlier start and a higher dose to reduce the excess mortality associated with ARF in critically ill patients.

Leukotriene B4 is involved in hemodialysis-associated neutropenia.

Biosynthesis of leukotriene B4 (LTB4) was studied in ten patients with end-stage renal failure undergoing chronic hemodialysis with a cuprophane membrane. As compared to healthy subjects the low basal plasma levels of LTB4 quantified by radioimmunoassay after extraction and purification by HPLC showed no significant difference. The time-course of LTB4 release after contact of the blood with the dialysis membrane without further in vitro stimulation was characterized by a rapid increase by about 500% within the first 10 min, appearing approximately at the same time as the known fall of white blood cell count which reaches its nadir after 20 min. Analysis of further release showed a decline of LTB4 biosynthesis to basal levels at the end of hemodialysis. These results indicate that activation of the 5-lipoxygenase pathway is involved in hemodialysis-associated leukopenia and may contribute to the alterations in neutrophils of patients with chronic dialysis therapy.

Multifocal primary amyloidosis of the airways: Case report and review of the literature.

Primary localized amyloidosis of the airways is an uncommon disorder characterized by amyloid deposits in the airway mucosa. In contrast to systemic amyloidosis other organs are not involved. Among the entities of airway amyloidosis, tracheobronchial amyloidosis is comparatively the most common subtype in the lower respiratory tract and laryngeal amyloidosis in the upper respiratory tract. The pathophysiology of localized airway amyloidosis is poorly understood. The clinical presentation is variable and often non-specific. No general consensus exists with regard to optimal treatment resulting in a variety of modalities used in clinical practice to manage this disorder. We report the case of a 50 year old woman with multifocal localized amyloidosis of the tracheobronchial tree and the upper airways. Tracheobronchial amyloidosis was treated with endoscopic debulking and external beam radiation, sinunasal amyloid deposits were surgically excised and are currently under surveillance. The importance of this extremely rare case lies in the multifocal presentation of an uncommon disorder requiring a multidisciplinary approach to offer optimal treatment including external beam radiation.

Reversal of diuretic-induced increases in serum low-density-lipoprotein cholesterol by the betablocker pindolol.

Seventeen patients with mild to moderate essential hypertension received during three consecutive 4 wk periods a matched placebo, the thiazide-like diuretic, clopamide in a low dosage of 5 mg/day, or this diuretic combined with the betablocker, pindolol in a low dosage of 10 mg/day. Compared to placebo conditions, clopamide monotherapy significantly increased serum low-density lipoprotein cholesterol (LDL-C) by 13% (p less than 0.025). Following addition of pindolol, serum LDL-C was restored to control values. These variations in serum LDL-C were unrelated to concomitant changes in blood pressure, plasma potassium, renin activity or aldosterone levels. Blood pressure in the supine position was reduced from 152/99 +/- 13/9 mm Hg (+ SD) to 141/93 +/- 15/7 mm Hg following diuretic-monotherapy and to 139/90 +/- 12/9 mm Hg following diuretic-betablocker combination treatment. These findings suggest that antihypertensive combination treatment with low doses of clopamide and pindolol is not only effective and well tolerated, but may also avoid the increase in serum LDL-C levels occurring when the thiazide-like diuretic is given alone.

Plasma cGMP level as a marker of the hydration state in renal replacement therapy.

We investigated, whether plasma cyclic guanosine 3':5'-monophosphate (cGMP) may be suited as a marker of hyperhydration in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). In 81 HD patients the levels of atrial natriuretic peptide (ANP) and cGMP were markedly elevated before HD (ANP: 165 +/- 11.1 pg/ml; cGMP 43.5 +/- 2.2 pmol/ml). Significantly lower values (P < 0.01) were found after HD (ANP: 97 +/- 8.4 pmol/ml; cGMP 19.5 +/- 1.5 pmol/ml). Twenty-three patients had cGMP levels above 20 pmol/ml after HD. Therefore "dry body weight" was reduced in these patients. This resulted in a "normalization" of cGMP values to a postdialytic range below 20 pmol/ml in the majority of patients. All seven patients with persistently high cGMP levels despite weight reduction had left sided heart failure. In 33 CAPD patients ANP was slightly lower than after HD (68 +/- 10.4 pg/ml), and the cGMP level (22.4 +/- 2.3 pmol/ml) was between pre- and postdialytic values in HD. In eight CAPD patients with clinical signs of hypervolemia plasma cGMP, but not ANP, was significantly elevated. We conclude that the plasma cGMP level appears to be a reliable marker for fluid overload in patients on renal replacement therapy with normal heart function.

Micropuncture studies on the renal handling of 2,4-diamino-6,7-dimethylpteridine.

The excretion of the diuretic substance DADMP (I,4-diamino-6.7-dimethylpteridine) and of DMP (6.7-dimethylpterin) was studied on single nephrons of the rat kidney using microperfusion and microinjection techniques. In the proximal tubule only DADMP was reabsorbed to a significant degree. Fractional reabsorption rate was independent of the load applied and the permeability constant was found to be 2.2 . 10(-4) cm . s-1. Similar results were obtained in nephrons in which the substances, with inulin, were injected from middle proximal tubular puncture sites and recovered in the urine. DMP appeared in the urine quantitatively and simultaneously with the injected inulin. DADMP recovery, however, was only 20--30% of the injected load during the injection period and after 2 h some 70% was recovered from the urine of both kidneys. The reabsorbed fractions were independent of the loads applied, which varied between 2 . 10(-13) mol . min-1 and 10(-9) mol . min-1. A comparison of the microperfusion and the microinfusion data suggests that the reabsorption of DADMP occurs predominantly in the proximal convolution, and it appears that the differences between the renal handling of DMP and DADMP are explicable by their different lipid solubilities.

Reversible MRI changes in a patient with uremic encephalopathy.

A 19-year-old patient on chronic ambulatory peritoneal dialysis experienced severe neurologic disturbances caused by uremia. Increased signal intensity was seen bilaterally in the cortical and subcortical areas of the occipital and parietal lobe on cranial magnetic resonance imaging (MRI). Insufficient peritoneal dialysis efficacy was documented and the patient was switched from peritoneal to hemodialysis. Cranial MRI indicated a marked regression of the lesions to nearly normal, confirming the diagnosis of uremic encephalopathy.

Successful management of polyneuropathy associated with IgM gammopathy of undetermined significance with antibody-based immunoadsorption.

Peripheral polyneuropathies associated with monoclonal IgM gammopathy of undetermined significance often have a progressive course and optimal treatment has not been established. We report on a patient diagnosed with polyneuropathy associated with benign IgM gammopathy, who was successfully treated with antibody-based immunoadsorption only. The neurological symptoms of the patient improved continuously over six months of treatment. Controlled trials should be performed to define this indication for antibody-based immunoadsorption therapy.

Hypertension induced by recombinant human erythropoietin (rHU-EPO) can be prevented by indomethacin. Pathogenetic role of cytosolic calcium.

Hypertension complicating the therapy of renal anemia with rHU-EPO is characterized by an increase in total peripheral vascular resistance, but the mechanisms underlying arteriolar vasoconstriction remain unclear. To assess the role of altered cellular calcium metabolism, resting platelet cytosolic calcium was measured in 12 previously normotensive patients with end-stage renal disease before and after 12 weeks of EPO-therapy, after 12 weeks of combined antihypertensive pharmacotherapy of EPO-induced hypertension, and after 12 weeks of concurrent administration of EPO and indomethacin. Patients with EPO-induced hypertension showed a significant raise in platelet calcium by comparison with calcium levels prior to EPO (179 +/- 15 vs 120 +/- 8 nmol/l), and there was a positive correlation between their blood pressure and platelet calcium levels (r = 0.9, p < 0.001). Antihypertensive therapy of EPO-induced hypertension resulted in a reduction of blood pressure and a reduction of platelet calcium to near normal levels (128 +/- 6 nmol/l). The non-steroidal antiinflammatory drug indomethacin prevented EPO-induced hypertension and EPO-associated alterations in platelet calcium. The results of the present study suggest that EPO-induced hypertension might be related to altered cellular calcium homeostasis. If EPO therapy induces alterations in calcium metabolism not only in platelets but also in vascular smooth muscle cells, these changes in calcium influx may contribute to arteriolar vasoconstriction during EPO therapy.

Characterization of subtypes of hypertension in CAPD patients by cyclic guanosine monophosphate.

OBJECTIVE: While most hypertensive patients with end-stage renal disease normalize high blood pressure with fluid removal by continuous ambulatory peritoneal dialysis (CAPD), there is a significant proportion of CAPD patients whose blood pressure can be controlled only by antihypertensive drugs. METHOD AND PATIENTS: To study the hypothesis that such patients are still volume overloaded, we used plasma cyclic guanosine monophosphate (cGMP) as a marker for hydration status. Thirty-two CAPD patients were divided into 3 groups: group 1, normotensive patients (n = 12); group 2, hypertensive patients who normalized their blood pressure with fluid removal (n = 12); group 3, hypertensive patients whose blood pressure was refractory to intensified fluid removal (n = 8). RESULTS: Mean cGMP levels were significantly higher in dialysis-sensitive hypertension (27 +/- 5 pmol/mL) than in dialysis-refractory hypertension (15 +/- 2 pmol/mL), or in normotensive patients (13 +/- 4 pmol/mL). Reduction of excess fluid in volume overloaded hypertensive CAPD patients resulted in a normalization of cGMP levels (14 +/- 8 pmol/mL), but did not affect this volume marker in patients with dialysis-resistant hypertension (10 +/- 4 pmol/mL). CONCLUSION: Plasma cGMP levels are elevated in volume overload-induced hypertension complicating CAPD. Hypertensive CAPD patients whose plasma cGMP levels are within normal limits have raised blood pressure refractory to volume removal. Our findings are consistent with the hypothesis that inadequate removal of excess volume plays a major role in a subset of patients with CAPD hypertension.

Preservation of residual renal function in dialysis patients: effects of dialysis-technique-related factors.

OBJECTIVES: Residual renal function (RRF) is of paramount importance to dialysis adequacy, morbidity, and mortality, particularly for long-term continuous ambulatory peritoneal dialysis (CAPD) patients. Residual renal function seems to be better preserved in patients on CAPD than in hemodialysis (HD) patients. We analyzed RRF in 45 patients with end-stage renal disease (ESRD), commencing either CAPD or HD, to prospectively define the time course of the decline in RRF, and to evaluate dialysis-technique-related factors such as cardiovascular stability and bioincompatibility. STUDY DESIGN: Single-center prospective investigation in parallel design with matched pairs. MATERIALS: Fifteen patients starting CAPD and 15 matched pairs of patients commencing HD were matched according to cause of renal failure and RRF. Hemodialysis patients were assigned to two dialyzer membranes differing markedly in their potential to activate complement and cells (bioincompatibility). Fifteen patients were treated exclusively with the cuprophane membrane (bioincompatible) and the other 15 patients received HD with the high-flux polysulfone membrane (biocompatible). MEASUREMENTS: Residual renal function was determined at initiation of dialytic therapy and after 6, 12, and 24 months. Dry weight (by chest x ray and diameter of the vena cava) was closely recorded throughout the study, and the number of hypotensive episodes counted. RESULTS: Residual renal function declined in both CAPD and HD patients, although this decline was faster in HD patients (2.8 mL/minute after 6 months and 3.7 mL/min after 12 months) than in CAPD patients (0.6 mL/min and 1.4 mL/min after 6 and 12 months respectively). It declined faster in patients with bioincompatible than with biocompatible HD membranes (3.6 mL/min vs 1.9 mL/min after 6 months). Eleven percent of the HD sessions were complicated by clinically relevant blood pressure reductions, but there were no differences between the two dialyzer membrane groups. None of the CAPD patients had documented hypotensive episodes. None of the study patients suffered severe illness or received nephrotoxic antibiotics or radiocontrast media. CONCLUSIONS: The better preservation of RRF in stable CAPD patients corresponded with greater cardiovascular stability compared to HD patients, independently of the membrane used. Furthermore, there was a significantly higher preservation of RRF in HD patients on polysulfone versus cuprophane membranes, indicating an additional effect of biocompatibility, such as less generation of nephrotoxic substances by the membrane. Thus, starting ESRD patients on HD prior to elective CAPD should be avoided for better preservation of RRF.