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.

Current practice of conventional intermittent hemodialysis for acute kidney injury.

The use of conventional intermittent hemodialysis (IHD) represents a mainstay of supportive care of patients with acute kidney injury (AKI). However, a number of fundamental questions regarding the optimal management of IHD remain unanswered after more than six decades of renal replacement therapy (RRT). This review summarizes current evidence regarding the timing of initiation of intermittent hemodialysis, the comparative outcomes (mortality and recovery of renal function), the prescription of the intensity of this therapy and discontinuation of dialysis. The way conventional IHD is performed has an impact on the outcome of sick patients with AKI. The value of regular education and training of those who provide IHD cannot be emphasized enough. However, we must be realistic in our expectations that no mode of RRT per se will substantially alter the excessive mortality of critically ill-patients with AKI.

[Acute kidney injury]. / Die akute Nierenschädigung.

Acute kidney injury plays a pivotal role in intensive care medicine and exerts crucial adverse effects on the course of the disease and overall prognosis of the critically ill patient. Intensive renal support, including initiation of earlier dialysis or maximal uremic toxin removal by higher dosage and frequency of renal replacement therapy, and individualized selection of modality were not able to decrease excessive mortality in this population. Systemic acute inflammation, mediated, at least in part, by cytokines, and not secondary uremic side effects, seems to have a major impact on nonrenal organ damage. Assessment of short-term outcome in critically ill patients who develop acute kidney injury may underestimate the true burden of disease. The overall survival at 5 years in patients discharged alive after severe acute kidney injury necessitating renal replacement therapy is only 20-30%, comparable to cancer patients. In addition, acute renal damage was identified as an independent risk factor for progression of chronic renal insufficiency. Current research focuses on strategies for the prevention of acute kidney injury and on the establishment of effective biomarkers for the early recognition and accurate diagnosis of subclinical renal damage.

Clinical cause of presumed acute tubular necrosis requiring renal replacement therapy and outcome of critically ill patients: post hoc analysis of a prospective 7-year cohort study.

BACKGROUND: Acute kidney injury (AKI) secondary to acute tubular necrosis (ATN) is common in critically ill patients, and causes significant morbidity and mortality. The underlying etiology of ATN can be divided into pure ischemic, pure nephrotoxic, and mixed causes. This post-hoc analysis of a prospective cohort study aimed to investigate whether the cause (pure vs. mixed) of ATN affects the short- and long-term outcome of critically-ill patients. METHODS: A total of 425 critically-ill patients with AKI secondary to clinically diagnosed ATN were divided into three groups according to the cause of ATN. Of these patients, 215 had mixed ATN, 203 had pure ischemic ATN, and seven had pure nephrotoxic ATN. All patients had one episode of AKI only. No patient had pre-existing chronic kidney disease. Patients were followed throughout their hospital stay (mortality rate, recovery of renal function at discharge) and up to 7 years thereafter. RESULTS: The three patient groups differed in their demographic and clinical characteristics. The in-hospital mortality rates were 55% in the presumably mixed-cause ATN group, 39% in the pure ischemic group, and 29% in the pure nephrotoxic group. Complete renal recovery at discharge was documented in five out of five surviving patients with nephrotoxic ATN (100%) and in 92 out of 124 surviving patients with pure ischemic ATN (74%), but only in 29 out of 97 patients with mixed ATN (30%). None of the surviving patients was lost during the 7-year follow-up. At the end of the observation period, 60% of the survivors of pure ATN, compared with 22% of the survivors of mixed ATN, were alive. After 7 years, 6% of the living patients with pure ATN had mild-to-moderate chronic kidney disease, whereas 38% of the mixed group patients had advanced CKD or end-stage renal disease. CONCLUSIONS: The cause of presumed ATN has a profound impact on short- as well as long-term outcomes of critically-ill patients with AKI requiring renal replacement therapy. The challenge for intensivists is to avoid further injury to the kidneys of these patients.

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.

[Partial clinical remission of chronic IgA nephropathy with therapy of tuberculosis]. / Partielle klinische Remission einer chronischen IgA-Nephropathie unter antituberkulotischer Therapie.

HISTORY AND CLINICAL FINDINGS: A 36-year-old patient suffered from repeated exsudative pleural effusions and renal insufficiency (serum creatinine 1.9 mg/dl) combined with glomerular erythrocyturia, proteinuria and renal hypertension. INVESTIGATIONS: The diagnosis of the underlying etiology of the pleural effusions was difficult in spite of a thorough diagnostic work-up. Pleural tuberculosis was finally detected by an interferon gamma release assay (IGRA). Kidney biopsy revealed mesangioproliferative glomerulonephritis, immunhistology showed mesangial IgA deposits. Renal insufficiency did not progress when blood pressure control was achieved. TREATMENT AND CLINICAL COURSE: The pleural effusions resolved permanently when antituberculous treatment was begun. Eight weeks after initiation of therapy normalization of kidney function (eGFR > 75 ml/min), resolution of hematuria and reduction of proteinuria were observed. CONCLUSIONS: This report of a partial remission of IgA nephropathy by treatment of pleural tuberculosis supports the hypothesis that there may be a causal relationship between mycobacterial infections and IgA nephropathy.

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.

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.

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.

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.

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.

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.

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.

Daily haemodialysis in acute renal failure. Old wine in a new bottle?

Acute renal failure (ARF) is a frequent complication in hospitalized patients. Despite advances in intensive care and renal replacement therapy, outcomes in ARF are distressingly poor. The high mortality of critically ill patients with ARF relates at least in part to fatal non-renal organ complications of ARF itself. However, adequacy of dialysis therapy in the setting of ARF is still in its infancy. At present, neither for intermittent haemodialysis (IHD) nor continuous renal replacement therapies specifically designed techniques have been developed or validated to measure the delivered dose of in ARF. Furthermore targets of optimal or required dose have not been defined. Problems intrinsic to ARF that hinder accuracy of dialysis dose measurements utilizing urea kinetic modelling include a lack of urea eubolism, uncertainty about the true patient total water volume and volume of distribution of urea, and significant access recirculation. The difference in prescribed versus delivered dialysis dose in patients with ARF undergoing IHD may exceed 20% and more and the majority of ARF patients will receive dialysis doses less than 1.2, which is considered the minimal level for end-stage renal disease patients undergoing regular dialysis. Nonetheless retrospective data from the Cleveland Clinic clearly demonstrate an influence of delivered Kt/V urea on survival in patients with intermediate ICU ARF severity scores. Our group prospectively compared outcomes in patients with ARF receiving IHD daily or on alternate days. Daily HD was associated with fewer dialysis-related hypotensive episodes, a shorter time and smoother course to recovery of renal function and a significantly reduced mortality compared to conventional HD. This article highlights also the facts that patients in the conventional group (the standard treatment in North America) treated every other day for 3 to 5 hours have been inadequately dialyzed, having a mean blood urea nitrogen (BUN) of 104 mg/dl and significantly more respiratory failure, sepsis, gastrointestinal bleeding or changes in mental status. To avoid significant underdialysis, conventional estimates of total body water should be increased by a factor of 1.2. Strategies associated with improved outcomes that have emerged thus far in ARF should aim at a time-averaged BUN of less than 60 mg/dl with IHD. IHD should be prescribed in varying frequency if necessary with daily sessions in hypercatabolic oliguric or heavy weight critically ill patients.

Ultrapure dialysis fluid lowers the cardiovascular morbidity in patients on maintenance hemodialysis by reducing continuous microinflammation.

The aims of our prospective 3-year investigation were (1) to clarify whether high C-reactive protein (CRP) levels are an intermittent or a continuous phenomenon in individual hemodialysis patients and (2) to evaluate a possible relationship between ultrapure dialysis fluid associated CRP levels and an increased prevalence of atherosclerosis in a group of 60 hemodialysis patients treated either with conventional (n = 38) or on-line-produced ultrapure dialysis fluid (n = 22). Primary end points of the study were angiographically confirmed cerebrovascular, cardiovascular, or peripheral vascular events. Measurements of the CRP levels were done every 3 months using a highly sensitive assay. The CRP levels were normal (<0.5 mg/dl) in 45 patients and raised in 15 patients at the time of recruitment. In 87% of the patients with normal CRP levels, ultrapure dialysis fluid was used. The CRP levels measured at recruitment and at various time points thereafter did not differ significantly within patient groups. However, patients with increased CRP concentrations experienced significantly more vascular events as compared with patients with normal CRP levels (11 events vs. 1 event; p < 0.001). The data indicate that continuous induction of acute-phase proteins represents a nontraditional vascular risk factor contributing to the development and progression of atherosclerosis in dialysis patients. Ultrapure dialysis fluid lowers cardiovascular morbidity by preventing/reducing chronic microinflammation.