I. Stefanidis

Imaging Modalities for Renal Artery Stenosis in Suspected Renovascular Hypertension: Prospective Intraindividual Comparison of Color Doppler US, CT Angiography, GD-Enhanced MR Angiography, and Digital Substraction Angiography

The aim of the study was to evaluate the diagnostic accuracy of Color Doppler US, CT Angiography (CTA), and GD-enhanced MR Angiography (MRA) compared with digital subtraction angiography (DSA) for the detection of renal artery stenosis in patients with clinically suspected renovascular hypertension. Fifty-eight patients with suspected renovascular hypertension were enrolled in the study. All patients underwent Color Doppler US, CTA and GD-enhanced MRA. DSA was the gold standard method for the number of renal arteries, existence and degree of stenosis, or evidence of fibromuscular dysplasia. DSA depicted 132 renal arteries, 16 stenoses, and 4 arteries with fibromuscular dysplasia. Color Doppler US failed to detect 1 main and 14 polar arteries. CTA depicted all main renal arteries and 7/16 polar arteries, but failed to detect stenosis in two accessory vessels. Likewise, MRA did not detect stenotic accessory renal arteries, depicted 9/16 polar renal arteries, but missed two main renal arteries. All methods depicted the four main renal arteries with fibromuscular dysplasia. The overall sensitivity, specificity, and positive and negative predictive accuracy were 75%, 89.6%, 60% and 94.6%, respectively, for color Doppler US; 94%, 93%, 71%, and 99%, respectively, for CTA; and 90%, 94.1%, 75%, and 98%, respectively, for GD-enhanced MRA. CTA and GD-enhanced MRA have comparable and satisfactory results with respect to the negative predictive accuracy of the suspected renal artery stenosis. The concept of an imaging algorithm including US as screening test when appropriate and CTA or MRA as the second step-procedure is suggested. Therefore, DSA may be reserved for cases with major discrepancies or therapeutic interventions.

Intradialytic aerobic exercise training ameliorates symptoms of restless legs syndrome and improves functional capacity in patients on hemodialysis: a pilot study.

We present the first study on the influence of exercise training on restless legs syndrome (RLS) in patients on hemodialysis (HD). Restless legs syndrome has been treated pharmacologically with satisfactory results; however, side effects and rebound phenomena have been reported. Intradialytic exercise training effectively counteracts uremia-induced catabolism; nevertheless, it remains unknown whether patients with RLS undergoing HD benefit from such programs. The aims of the current study were to evaluate the effect of 16-weeks aerobic exercise training in the severity of RLS and in the functional capacity and the quality of life of patients with RLS on HD. Fourteen patients on HD (four female, mean age 59 ± 16 years) with untreated RLS were assigned, according to their will, to either the exercise group (Ex-group, n = 7), and participated in a 16-week supervised intradialytic aerobic exercise training, or to the control group (Con-group, n = 7), and continued usual activities. Primary aim was to compare the International RLS (IRLS) study group rating scale, functional ability, and quality of life in baseline and the end of the 16 weeks. Exercise training reduced IRLS score by 42% (p = 0.02). Furthermore, it significantly improved indices of functional ability (p = 0.02), exercise capacity (p = 0.01), quality of life (p = 0.03), and sleep quality (p = 0.01). In the Con-group no changes were observed. In conclusion, aerobic exercise training is safe and efficacious in reducing RLS symptoms and improving quality of life in patients with RLS on HD.

Acute renal failure after antibiotic-impregnated bone cement treatment of an infected total knee arthroplasty

Antibiotic-impregnated cement is used frequently in revision procedures of infected total hip and knee arthroplasties. Local antibiotic treatment is as effective as the use of systemic antibiotics. The purpose of such treatment is to provide high tissue concentrations of antibiotics and minimize systemic toxicity, especially nephrotoxicity. Though antibiotic-impregnated cement is considered safe in terms of nephrotoxicity, two cases that have implicated aminoglycoside-impregnated cement in acute renal failure (ARF) after surgery for an infected total knee arthroplasty (TKA) have been reported [Curtis et al. 2005, Van Raaij et al. 2002]. Two more cases of postoperative ARF after use of combined tobramycin- plus vancomycin-impregnated cement, this time in total hip arthroplasty, have been recently reported [Patrick et al. 2006]. We report a case of ARF in a 61-year-old patient with a history of diabetes mellitus and hypertension after treatment of a febrile infection of a TKA with combined gentamicin- plus vancomycin-impregnated cement. The ARF could not sufficiently be attributed to other causes and though serum concentrations of antibiotics obtained from the 8th postoperative day and thereafter were far below the trough levels associated with nephrotoxicity, gentamicin and vancomycin seem to have contributed significantly to ARF in our case.

A case of membranous nephropathy associated with Sjögren syndrome, polymyositis and autoimmune hepatitis.

Sjögren syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, especially lacrimal and salivary. The immunologic process which occurs in this syndrome is B cell hyperactivity, which results in production of autoantibodies and immune complexes. SS can exist as a primary disorder or in association with other autoimmune processes. A usually mild, proximal and insidious inflammatory myopathy can occur in patients with SS with a broad clinical and pathological spectrum. Interstitial nephritis with mild proteinuria and tubular dysfunction is the most common renal manifestation of SS, but glomerular involvement due to immune complex deposition may also rarely occur [Goules et al. 2000]. There is an association of SS with hepatic abnormalities, as evidenced by abnormal liver biochemical tests or histological characteristics of primary biliary cirrhosis (PBC), portal tract fibrosis, or autoimmune hepatitis [Abraham et al. 2004]. The pathogenetic mechanism of liver involvement in SS is not clear, but it is possible that hepatic and salivary gland damage share a similar pathology. The combination of Sjögren syndrome with kidney, liver and muscle involvement in one entity is extremely rare and data in the literature are remarkably sparse. We present a case of a 43-year-old female patient suffering from SS accompanied by polymyositis, membranous nephropathy and autoimmune hepatitis.

Restless legs syndrome in hemodialysis patients: an epidemiologic survey in Greece

BACKGROUND Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an uncontrolled need to move extremities accompanied by unpleasant sensations, which frequently leads to sleep disturbances. In hemodialysis (HD) patients, the previously reported RLS prevalence varied enormously, between 6% and 60%. In our study, we investigated the RLS prevalence in HD patients for the first time in Greece. METHODS A continuous sample of HD patients was studied between January and September of 2010 in six dialysis units in Greece. RLS diagnosis was based on the essential clinical criteria of the International RLS Study Group (IRLSSG). The standardized incidence ratio (SIR) for RLS in HD patients was calculated in comparison to data from a recent survey of the general population in Greece. RESULTS In our study of 579 HD patients in Greece (236 women; mean age, 65±13years), the prevalence of RLS was elevated in comparison to the general population (26.6% vs 3.9%), with an SIR of 5.4 (95% confidence interval [CI], 4.6-6.3). In the fully adjusted model, the risk for RLS in HD patients was reduced in older age (odds ratio [OR], 0.98 [95% CI, 0.96-0.99]) and increased in women (OR, 1.60 [95% CI, 1.05-2.43]) in cases with elevated levels of β2 microglobulin (OR, 1.15 [95% CI, 1.01-1.32]) and intact parathormone (iPTH) (OR, 1.30 [95% CI, 1.08-1.56]). CONCLUSION A high RLS prevalence was recorded in a large HD population in Greece, clearly suggesting the need for enhanced awareness of RLS in nephrology. The RLS risk was increased in women and in younger HD patients as well as in those with elevated β2 microglobulin and iPTH levels.

The diabetic foot in end stage renal disease.

Diabetic foot lesions remain a major cause of morbidity in patients with renal failure, especially those on dialysis. Foot complications are encountered at a more than twofold frequency in diabetic patients with end-stage renal disease, and the rate of amputations is 6.5–10 times higher in comparison to the general diabetic population. The causal pathways of the diabetic foot in renal failure are multiple and inter-related. Three major pathologies—neuropathy, ischemia, and infection—are the main contributory factors. Increased awareness of this condition and careful clinical examination are indispensable to avoid serious complications. Appropriate management needs to address all contributory factors. Treatment options include revascularization, off-loading to relieve high-pressure areas, and aggressive control of infection. Equally important is the collaboration between health care providers in a multidisciplinary foot care setting. Moreover, patient education on the measures required to achieve both primary and secondary prevention is of great value. Certainly, technical innovations have made considerable progress possible, but there is a need for further improvement to reduce the number of amputations.

Skeletal muscle atrophy: disease-induced mechanisms may mask disuse atrophy

Disuse atrophy is the loss of skeletal muscle mass due to inactivity or lower than ‘normal’ use. It is not only a furtive component of the ‘modern’ sedentary lifestyle but also a part of numerous pathologies, where muscle loss is linked to disease specific and/or other toxicity factors, eventually leading to wasting (cachexia). Whether disuse-or-disease induced, muscle loss leads to weakness and metabolic comorbidities with a high societal and financial cost. This review discusses the intricate network of interacting signalling pathways including Atrogin-1/MAFbx, IGF1-Akt, myostatin, glucocorticoids, NF-kB, MAPKs and caspases that seem to regulate disuse atrophy but also share common activation patterns in other states of muscle loss such as sarcopenia or cachexia. Reactive oxygen species are also important regulators of cell signalling pathways that can accelerate proteolysis and depress protein synthesis. Exercise is an effective countermeasure and antioxidants may show some benefit. We discuss how the experimental model used can crucially affect the outcome and hence our understanding of atrophy. Timing of sampling is crucial as some signalling mechanisms reach their peak early during the atrophy process to rapidly decline thereafter, while other present high levels even weeks and months after study initiation. The importance of such differences lays in future consideration of appropriate treatment targets. Apart from attempting to correct defective genes or negate their effects, technological advances in new rational ways should aim to regulate specific gene expression at precise time points for the treatment of muscle atrophy in therapeutic protocols depending on the origin of atrophy induction.

Influence of recombinant human erythropoietin therapy on plasma endothelin-1 levels during hemodialysis.

The correction of anemia with human recombinant erythropoietin (rHuEPO) in end stage renal disease is associated with hypertension in about one third of hemodialysis patients. The pathogenesis of the rHuEPO-induced hypertension is still uncertain, though evidence of the involvement of endothelial cells has emerged. The aim of this study was to determine plasma endothelin-1 during hemodialysis and to compare the endothelin-1 levels in hemodialysis patients with and without rHuEPO substitution. Nineteen stable patients (13 male and 6 female, mean age 62 ± 11 years) with end stage renal disease were studied. Cuprophan dialysers (GFS 12®, Gambro, Lund, Sweden) were used for hemodialysis in all cases. rHuEPO (40U/kg s.c.) was administered to 10 patients. Blood pressure (BP; RR mmHg) and blood volume changes (ΔBV; hemoglobinometry %) were serially measured. Samples were taken before and every hour during hemodialysis. Plasma endothelin-1 was measured by ELISA (R&D Systems, Minneapolis, USA) and corrected for hemoconcentration. Endothelin-1 concentration was elevated before commencement of hemodialysis (1.16 ± 0.36 pg/ml) when compared to healthy controls (ref. 0.3 - 0.9) and increased to 1.47 ± 0.51 pg/ml by the end of the session (p<0.05). In patients under rHuEPO-substitution plasma endothelin-1 was higher when compared to patients without substitution before (1.25 ± 0.3 vs. 1.05 ± 0.3 pg/ml) and at the end of HD (1.62 ± 0.5 vs. 1.28 ± 0.3 pg/ml, p<0.05). There was no difference in BP and ΔBV between the two groups during treatment. Plasma endothelin-1 was higher in hemodialysis patients and there was a continuous rise in plasma endothelin-1 during a session. Comparison of two groups of hemodialysis patients with and without s.c. rHuEPO-replacement treatment revealed a significantly higher plasma endothelin-1 concentration in patients with s.c. rHuEPO treatment. However, the elevated endothelin-1 levels were not accompanied by arterial hypertension.

Group B Streptococcus (Streptococcus agalactiae) peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD).

Streptococcus agalactiae typically induces serious infections in pregnant women and newborns. Nonpregnant adult patients can also be infected and mortality rate exceeds 40%. CAPD peritonitis is very rarely induced by S. agalactiae. Seven cases have been described previously and all had a very severe course, which included bacteremia, septic shock and death. A 27-year-old male with end-stage renal disease due to membranoprolipherative glomerulonephritis type I, who was on CAPD for 17 months, was admitted with the clinical and laboratory picture of CAPD peritonitis. Severe abdominal pain, shaking chills and fever 38.5 microC were also observed at presentation. Streptococcus agalactiae was isolated from the peritoneal fluid and blood culture was sterile. Under treatment with ceftazidime and tobramycin (i.p.) and vancomycin (i.v.) cultures became negative after 48 hours, abdominal symptoms resolved after 12 days and WBC count in the dialysate normalized after 14 days. As a possible source of infection the patients partner was shown to be a vaginal carrier of a clone of S. agalactiae identical to that isolated in the peritoneal fluid. S. agalactiae is a rare cause of CAPD peritonitis with potentially very serious consequences. Anal or genital tract colonization is, in general, the source of contamination with S. agalactiae. The microbiological findings in the case presented here suggest that colonization of the patient or of his close environment may be important in the pathogenesis of S. agalactiae-induced CAPD peritonitis.

Restless legs syndrome does not affect 3-year mortality in hemodialysis patients

OBJECTIVE Uremic restless legs syndrome (RLS) has been related to an enhanced mortality of hemodialysis (HD) patients. In the general population studies of this association have yielded inconsistent results. The aim of the present study was to re-evaluate the relationship of RLS and mortality in HD patients. METHODS We recorded the 3-year mortality in 579 HD patients after assessment for RLS symptoms. This population has been previously evaluated for the prevalence of RLS, according to the essential criteria of the International RLS Study Group. Mortality data were acquired from the national end-stage renal disease registry. Survival probability was calculated by the Kaplan-Meier method and analyzed by the log-rank test. For multivariate survival analysis, we implemented a Cox regression model. RESULTS During the 3-year follow-up, we documented 118 deaths. Mortality was 15.6% in patients with RLS and 22.3% in patients without RLS (p =  0.079). According to the Cox regression analysis, there was no significant association between RLS and 3-year mortality, either in an age- and gender-adjusted model (hazard ratio [HR] = 0.772, 95% confidence interval [CI] = 0.488-1.219, p = 0.267) or in a multivariate adjusted model (HR = 0.667, 95% CI = 0.417-1.069, p = 0.092). CONCLUSION Diagnosis of RLS according to the essential criteria of the International RLS Study Group does not seem to influence the 3-year mortality in HD patients. Our findings are in contrast to those in some previous reports, and reinforce the need for further studies of RLS and mortality in HD.