Cardiorenal syndrome at different stages of chronic kidney disease.

The central concept of the cardiorenal syndrome (CRS) is that the heart and the kidney should be regarded not solely as individual organs but rather as a dipole with multiple interconnections. The interplay between the heart and the kidney seems complex and multifactorial: cardiac output, regulation of extracellular volume, blood pressure and renal sodium handling are the major parameters that determine the crosstalk between the 2 organs. These basic parameters are controlled through mediators (renin-angiotensin system, endothelin) and the relevant antagonists (natriuretic peptides). Recently, it has been shown that the nitric oxide / reactive oxygen species balance, sympathetic nervous system activation and the presence of systemic inflammation aggravate atherosclerosis, promote structural alterations in left ventricular geometry and favor progression of renal disease. Although the prevalence of the CRS is high, major clinical trials for heart failure have only partially addressed this issue. The present review tries to dissect the role of various components of the CRS in a way that could potentially facilitate the implementation of specific therapeutic strategies. The multiple factors that participate in the pathogenesis of this syndrome are studied in detail in an effort to better understand this syndrome and address effectively its various components, since a holistic approach could (ideally) alter the syndrome's course and hence ameliorate the prognosis of the CRS.

Incidence and risk factors of coronary artery disease in patients on chronic hemodialysis.

Aim of the study was to estimate the incidence of coronary heart disease (CAD) in patients (pts) with end stage renal disease (ESRD) maintained on chronic hemodialysis (HD) and its association with the presence of predisposing factors. The study included 171 dialysis pts (107 male (M) and 64 female (F)). Mean age of pts was 67+/-13 years, mean time on dialysis 52.7+/-44 months and Body Mass Index (BMI) 25.9+/-3.7 kg/m2. Fifty pts (29.2%) were clinically diagnosed with CAD. The diagnosis was established by coronary angiography in 24 (48%) and in 26 by combined dipyridamole-exercise thallium imaging (52%). Pts' data in association with the development of CAD that were recorded included age, sex, smoking habits, hypertension, obesity, the presence of diabetes mellitus (DM), hyperlipidemia, anemia, low albumin levels, secondary hyperparathyroidism (SHP), the presence of chronic inflammation, as evidenced by the presence of elevated levels of CRP and hyperhomocysteinemia. There was a statistically significant association of increasing age and CAD (p<0.0001). Relative risk (RR) was significantly increased i) in male pts compared to female pts (RR: 8.56, p<0.001), ii) in anemic pts compared to pts with hemoglobin levels< or =11 g/dL (RR: 8.26, p<0.0001), iii) in obese pts compared to pts with BMI < or =30 (RR: 5.09, p<0.005) and iv) in pts with increased levels of homocysteine compared to pts with levels of homocysteine <15 |IM (RR: 4.14, p<0.0001). Using linear regression analysis, CAD was associated with the inadequacy of HD (r = - 0.05, p<0.0001), time on HD (r =0.04, p =0.012) and increasing age (r =0.24, p<0.001). There was no statistically significant association between CAD and the presence of the other traditional risk factors. The incidence of CAD in dialysis pts is significantly increased with age, male sex, obesity, time on dialysis, the presence of anemia, hyperhomocysteinemia and inadequacy of HD.

Prevalence of the metabolic syndrome in hemodialysis.

BACKGROUND: Recently, the concept of the metabolic syndrome (MS) has emerged in an effort to group and study as a whole several cardiovascular risk factors. The definition of the metabolic syndrome requires the presence of 3 or more of the following parameters: high blood pressure (>/= 130/85), waist circumference >102 cm in men and >88 cm in women, HDL<50 mg/dL in men and <40 mg/dL in women, serum triglycerides >150 mg/dL and fasting blood glucose >/= 110 mg/dL. OBJECTIVES: To investigate the prevalence of the MS and the specific patient characteristics in a cohort of hemodialysis patients. MATERIALS AND METHODS: 102 stable patients on maintenance hemodialysis (63 male/39 female with a mean time on dialysis of 57.19 +/- 47.16 months) were studied for 12 months. RESULTS: The prevalence of the MS is high (56.25%) during the first year on dialysis and gradually declines (44.8% from 2-5 years and 29.7% for >5 years). In total 41/102 patients had MS (40.19%); 28/41 were men (68.29%) and 13/41 women (31.7%). The prevalence of MS in males was 44.4% (28/63) and 33.3% (13/39) in females, while the most frequent combination of risk factors in MS patients was high blood pressure-high waist circumference-high levels of serum triglycerides (36.58%). Serum triglycerides >150 mg/dL is the most frequent component of the MS both in well-nourished patients and according to the duration of dialysis (58.53% for 0-5 years and 19.51% for >5 years on dialysis). MS patients had a better nutritional status and were on dialysis for less time than their non-MS (NMS) counterparts. Actual or anamnestic cardiovascular events and infections did not differ between the 2 groups. CONCLUSIONS: Our study provides new data concerning the prevalence of the MS and the specific patient characteristics in a hemodialysis population. The prevalence of MS in hemodialysis patients is high (40.19%) and seems to reflect a state of good nutrition compared to patients without the MS. Furthermore, the MS is more common in the first years of dialysis (42.46+/-34.29 months) than later on (67.25+/-52.15 months) probably reflecting the long term consequences of the hemodialysis treatment. Our results also indicate that although patients in the MS group were well-nourished and for a shorter time on dialysis, they were not protected from cardiovascular disease and infections. Our study provides new data concerning both the prevalence of the MS and a variety of patient characteristics in a hemodialysis population. Further research and a larger number of patients are required in order to clarify the precise role of this syndrome in patients on MHD.

Uremic pruritus.

Renal itch is a localized or generalized itch, affecting patients with Chronic Renal Failure, where there is no primary skin disease and no systemic or psychological dysfunction that might cause pruritus. Uremic pruritus (UP) is an unpleasant sensation, rarely appearing in earlier stages of chronic kidney disease. Renal transplantation is the definite solution for that problem. The prevalence of UP has been reduced during the last years, possibly, due to a more efficient dialysis, with more biocompatible filters. During the last decades a big number of substances were considered to be etiologic factors of UP, and an even bigger number of therapeutic substances appeared with promising potentials and conflicting results in the course of their use. The main reason for this disorientation is the lack of sound evidence on the pathogenetic mechanisms that may potentiate UP. 'Inflammatory' and 'opioid' hypothesis are the best studied and the reduction of UP is a fact. Nevertheless the mechanisms of the pathogenesis of UP are still under investigation and a long way has to be done in order to achieve more definite results.

Pregnancy outcome in women with pre-existing lupus nephritis.

The aim of the present study was to assess the fetal and maternal outcome in a cohort of patients with lupus nephritis. Twenty-four pregnancies in 22 women with lupus nephritis occurring between 1991 and 2000 were analysed retrospectively. Lupus nephritis was biopsy proven before pregnancy in all cases. Women were followed from the beginning of pregnancy up to 6 months postpartum. Close fetal-maternal monitoring and frequent laboratory investigations were applied routinely to all patients. All women were prescribed steroid therapy from the beginning of the pregnancy. There were 18 live births, four spontaneous abortions and two stillbirths. Of the 18 live births, 14 were premature and four were term deliveries, representing a 25% fetal loss rate and 58% prematurity rate. There were two fetuses with congenital heart block. We recorded hypertension in 42%, proteinuria in 50% and pre-eclampsia in 25% of our patients. Proteinuria was irreversible in four cases. No maternal deaths or postpartum exacerbation of the disease were recorded in the study period. All renal flares were reversed postpartum. Patients positive for antiphospholipid antibodies had a worse perinatal outcome. Hypertension, proteinuria and antiphospholipid antibodies appear to be associated with adverse perinatal outcome and pregnancy complications. Pregnancy is not contraindicated in women with lupus nephritis, but is associated with significant fetal and maternal risks.

Unusual clot formation following insertion of central double lumen catheter for hemodialysis.

BACKGROUND: We report a case of a patient with chronic renal failure (CRF) due to fibrillary glomerulonephritis, who was admitted to our Hospital with fever accompanied by chills, of two days duration. Due to aggravation of his CRF, accompanied by severe metabolic acidosis, an internal jugular double lumen central vein catheter was inserted, through which he was hemodialyzed. METHODS: Blood cultures were negative. The catheter was removed and the tip was cultured; it revealed colonization with hemolytic Staphylococcus sensitive to vancomycin and metilmycin. They were both given to the patient with excellent results. Trans-thoracic and trans-esophageal echocardiography revealed a clot in the right atrium with an abnormal circumference, connected to the tip of the second catheter. Anticoagulants were administered (calsium nadroparin, converted seven days later to acenocoumarol) and the size of the clot was significantly reduced. RESULTS: The case is presented in order to prove the significant contribution of trans-esophageal echocardiography as a non-invasive imaging technique for the detection of a clot in the right atrium and the impressive influence of appropriate therapeutic management in saving the patient's life and reducing the clot size. CONCLUSIONS: The trans-esophageal echocardiogram provides invaluable information concerning the evolution, development and regression of right atrium clots formed at the tip of jugular catheters.

Association of serum nitric oxide levels with depressive symptoms: a study with end-stage renal failure patients.

BACKGROUND: Nitric oxide (NO) is a soluble gas produced by the activity of an enzyme found in neurons. It has been implicated in a great number of normal physiological functions (such as noradrenaline and dopamine release, memory and learning, regulation of the cerebrovascular system, modulation of wakefulness, modulation of nociception, olfaction, food intake and drinking) as well as pathologies (Alzheimer's, Huntington's disease, cerebral ischemia, stroke). Two reports have addressed the involvement of NO in depression. METHODS: The objective of the study was to examine the association between NO and specific depressive symptoms. For this purpose, in a sample of 28 end-stage renal failure patients (who have increased NO levels), we tested the hypothesis that the subgroup of patients with these specific depressive symptoms was differentiated from the patients without these symptoms with regard to serum levels of NO metabolites. The depressive symptoms were assessed using the Zung self-rating scale. RESULTS: Our study revealed an association of NO with the following depressive symptoms: sexual dysfunction, weight loss, psychomotor retardation, indecisiveness and irritability. CONCLUSION: The association between NO system and symptoms of depression does not necessarily imply a pathogenetic association between NO and depressive disorder. Further research is needed to verify these findings and study their possible pathogenetic implications.

Membranous glomerulonephritis: a morphometric study.

Archival material from 45 renal biopsies with a diagnosis of idiopathic membranous glomerulonephritis (MGN) were studied by computer-aided image analysis in order to evaluate the prognostic significance of glomerular and interstitial morphometry in MGN. The control group consisted of thirty seven normal renal biopsy specimens. The surface area, the perimeter, the major axis length and the shape factor of renal glomeruli as well as the percentage of the interstitial fibrosis were measured. All the morphometric parameters related to the size of glomeruli had significantly higher values in the patient group (p = 0.000 for all the parameters). However, no significant difference of the glomerular size between different stages of MGN was observed. In contrast, the percentage of interstitial fibrosis increased as the MGN stage rose (median values: 10.3% in stage 1, 14.2% in stage II, 26.9% in stage III, 28.9% in stage IV and 34.2% in stage V, Kruskal-Wallis ANOVA H = 37.645, p = 0.000). In the multivariate analysis the percentage of interstitial fibrosis was the only independent prognostic factor (p = 0.013). Our findings suggest that, in membraneous glomerulonephritis, the interstitial fibrosis increases as the MGN stage progresses, while the size of renal glomeruli has increased at a very early stage of the disease. This fact may indicate that interstitial fibrosis, not glomerular lesions, is mainly responsible for the reduction of renal function.

Complications of vascular access in hemodialysis (HD)--aged vs adult patients.

Reports on the success of permanent vascular access in elderly HD patients vary considerably. We reviewed the records of 149 patients [62F and 87M] aged 20-89 years old (median 59) who were on hemodialysis for 6-242 (49 median) months, and had undergone 202 vascular access procedures (177 Cimmino-Brescia fistulae and 25 PTFE grafts). Patients were divided into two groups according to the age they started HD. Group A: 48 patients, over 60 years old (range 60-83; median 70) on HD for 43.5, (6-140) months. Group B: 101 patients, under 60 years old, range (15-59) median 46, on HD for 54 (6-242) months. There were no differences between the two groups in terms of gender, primary renal disease, (except polycystic kidney disease), Hct and EPO administration. The initial choice of vascular access, the complications and the technique survival were examined in both groups. Cimmino-Brescia fistulae were used as the first choice of vascular access in all patients except one in group B. PTFE-grafts were the second or third choice in 7/48 (group A) and 15/101 (group B) (p: NS). The only reason for technique failure was vascular thrombosis in both groups (11/48 group A and 31/101 group B p: NS). Other complications were: aneurysms (10/48 and 14/101, p: NS), infections (0/48 and 2/101 p: NS) and edema (0/48 and 6/101, p: NS). Five-year technique survival of the first AV fistula in the two groups was 35% and 45% respectively (log-rank test, p: NS). These findings suggest that: a) A.V. fistula is the first choice of vascular access in aged HD patients; b) There is no difference in vascular access complications across age groups; c) Survival of the first A.V. fistula is independent of age.

Successful use of recombinant human erythropoietin in a pregnant woman with lupus nephritis.

Recombinant human erythropoietin (r-HuEPO) is broadly accepted as treatment for anemia in dialysis and nondialysis patients with chronic renal failure, but data regarding the safety and efficacy of this drug in pregnancy are limited. Maternal and fetal problems have been reported to be associated with anemia during pregnancy. On the other hand, anemia is a frequent feature of systemic lupus erythematosus. We report the successful use of r-HuEPO in a young woman with lupus nephritis complicated by severe anemia during pregnancy. Additional studies should be encouraged to confirm the safety of r-HuEPO therapy during pregnancy.

Procollagen type-I in the serum and dialysate of continuous ambulatory peritoneal dialysis patients.

Procollagen-I carboxylterminal extension peptide (PICP) was determined in the serum and dialysate of 26 continuous ambulatory peritoneal dialysis (CAPD) patients and in the serum of 11 healthy controls. PICP serum levels were significantly higher in CAPD patients than in healthy controls (p < 0.001). There was no correlation between serum PICP levels and those of calcium, phosphorus, magnesium, alkaline phosphatase, osteocalcin, and intact parathyroid hormone (iPTH). Serum and dialysate levels of osteocalcin and iPTH showed a significant correlation (p < 0.001). The dialysate-to-serum PICP ratio in 21 patients was lower than 1.0. In the remaining 5 patients, however, the above ratio was higher than 1.0. We conclude that in CAPD patients serum PICP levels do not correlate with biochemical parameters of renal osteodystrophy. A dialysate-to-serum PICP ratio above 1.0 could implicate an increased local peritoneal fibroblastic activity and could be a useful marker of peritoneal fibrosis in CAPD.

Elimination kinetics of mezlocillin in normal and impaired renal function including the effects of dialysis.

The kinetics of 6-[(R)-2-[3-methylsulfonyl-2-oxo-imidazolidine-1-carboxamido]-2-phenyl-acetamido]-penicillanic acid sodium salt (mezlocillin, Baypen) in renal failure were studied in 23 patients, given 5 g as i.v. infusion. Serum half-lives (t1/2) were around 60 min in normal renal function, 90 to 120 min in patients with a creatinine clearance (Clcr) of 30-60 ml/min, 160 to 190 min at a ClCr of 15 to 30 ml/min and 6 to 14 h in patients with a ClCr below 10 ml/min. There was a linear correlation between serum creatinine and t1/2. Peritoneal dialysis reduced t1/2 to 3 to 4 h and during haemodialysis t1/2 was 1.4 to 2 h with a mean extraction ratio of 0.25. Levels in urine were very high, even in advanced renal failure and the recovery rate was around 60% of dose in normal renal function, but less in renal failure, being only 10-20% at a ClCr of less than 10 ml/min. Levels in peritoneal dialysate fluctuated between 20 and 30 microgram/ml for 4 to 6 h after the infusion, falling slowly but still averaging 10 to 15 microgram/ml after 18 h. Dosage regimens are proposed for various situations in impaired renal function.