Paolo Gilli

Prevalence of Infected Patients and Understaffing Have a Role in Hepatitis C Virus Transmission in Dialysis

To assess hepatitis C virus (HCV) incidence rates and identify determinants of infection among hemodialysis patients, a multicenter study was conducted in 58 units in ITALY: An initial seroprevalence survey was conducted among 3,492 patients already on hemodialysis therapy as of January 1997 and among an additional 434 patients who began dialysis up to January 1998. HCV antibodies were assessed by third-generation enzyme immunoassays. Patients testing seronegative at baseline were enrolled into a 1-year incidence study with serological follow-up at 6 and 12 months. For patients who seroconverted, an HCV RNA assay was performed on stored baseline samples to confirm new infection. A nested case-control study was subsequently performed to investigate potential risk factors. For each incident case, three controls negative for both HCV antibodies and HCV RNA were randomly selected. At enrollment, HCV seroprevalence was 30.0%. During follow-up, 23 new HCV cases were documented, with a cumulative incidence of 9.5 cases/1,000 patient-years. By logistic regression analysis, an increased risk for HCV infection emerged for patients attending the dialysis units with a high prevalence of HCV-infected patients at baseline (odds ratio [OR], 4.6) and for those attending units with a low personnel-patient ratio (OR, 5.4). Among extradialysis factors, a history of surgical intervention in the previous 6 months (OR, 16.7) significantly increased HCV risk. These findings suggest that the combination of understaffing and a high level of infected patients in the dialysis setting increases the risk for HCV nosocomial transmission. This is likely related to an increased likelihood for breaks in infection control measures.

Continuing loss of vertebral mineral density in renal transplant recipients

This cross-sectional study examined bone abnormalities by digital radiography, bone densitometry and biochemical tests in 44 clinically asymptomatic renal transplant recipients 6–195 months after renal transplantation. Abnormal radiographs were obtained in 40 of the 44 patients. Dual-energy X-ray absorptiometry (DXA) performed at the lumbar spine (L2–L4)/showed a negative Z score in all patients, ranging from −1 to −1.9 in 28 patients and less than −2.0 in 16 patients. The severity of osteopenia increased with the length of time after transplantation and there was a significant correlation with parathyroid hormone values in patients with normal and low glomerular filtration rates. Our data suggest that decreased bone density values (Z score less than −2) are present in about one-third of patients with renal transplants. Bone loss appears to continue after transplantation. Steroid therapy and immunotherapy are probably the cause of this bone loss. Bone mineral measurements alone are helpful in identifying asymptomatic patients with low bone mass after transplantation.

Skin Lesions in Kidney Transplant Recipients

A complete examination of the skin was performed in 53 kidney transplant recipients. Cutaneous lesions were detected in almost all patients. Papillomavirus infections, premalignant and malignant lesions represent the greatest risk for these patients. Our study underlines the importance of a continuous observation to facilitate early diagnosis and treatment of these lesions.

Destructive spondyloarthropathy and radiographic follow-up in hemodialysis patients

Nine patients undergoing regular dialytic treatment for more than 60 months showed clinical and radiologic features of a noninfective and destructive spondyloarthropathy. The cervical spine was most affected (100%), followed by the dorsal (three patients, 33.3%) and the lumbar spine (two patients, 22.2%). Typically, radiographs and CT scans revealed narrowing of intervertebral spaces, with destruction or sclerosis of the subchondral bone of the vertebral plate.Autopsy was performed on three patients; histologic study demonstrated the presence of large amyloid deposits containing β2-microglobulin (β2-m) in the discs and peridiscal ligaments.A radiographic follow-up of the cervical spine was performed in seven patients after a period of 12 months and showed that the bone destruction in DSA is very rapid and progressive. The lower biocompatibility of the cuprophan membranes of dialyzers is probably the factor most responsible for hyperproduction of β2-m and subsequently osteoarticular deposition of a new type of amyloidosis.

Loss of the Nocturnal Increase in Plasma Concentration of Atrial Natriuretic Peptide in Hypertensive Chronic Renal Failure

Diurnal change of plasma atrial natriuretic peptide (ANP) concentration was investigated in 12 patients with hypertension due to chronic renal failure (CRF) and in 12 patients with essential hypertension (EH) of comparable degree. Blood pressure (BP) monitoring was performed at 15-min intervals, while peripheral blood samples were obtained at 4-hour intervals starting from 8.00 h. The mean 24-hour plasma levels (+/- SEM) of ANP were 24.3 +/- 1.8 pmol/l in EH and 23.4 +/- 1.2 pmol/l in CRF. In EH, plasma ANP concentration was highest at 4.00 h (33.5 +/- 0.8 pmol/l) and lowest at 16.00 h (15.5 +/- 0.6 pmol/l). In CRF, no significant circadian change was present (22.2 +/- 3.1 and 20.4 +/- 3.6 pmol/l, respectively), and the nocturnal fall in BP was lost. Our data demonstrate that in CRF the loss and possible reversal of the nocturnal decline in BP is associated with the disappearance of any significant circadian variation in the circulating concentrations of ANP. These findings suggest a role for ANP in the alteration of BP variability of CRF, possibly mediated by autonomic dysfunction, and are further evidence for the existence of a relation between the circadian rhythms of ANP and BP.

Erythropoietin and Cardiocirculatory Condition in Aged Patients with Chronic Rena l Failure

Background/Aim: The clearest benefit of recombinant human erythropoietin (rHuEPO) in end-stage renal disease is a substantial reduction in transfusion dependency and an improved quality of life. In this report, we describe the efficacy of weekly subcutaneous administration of rHuEPO in 11 elderly patients with anemia secondary to chronic renal failure. Methods: The role of rHuEPO therapy in increasing the patient’s quality of life and in decreasing the hospitalization rates secondary to cardiac morbidity was verified in 11 elderly patients (age range between 66 and 85 years) with anemia due to chronic renal failure. The mean hemoglobin level at the beginning of the study was 8.2 ± (SD) 0.7 g/dl, and the serum creatinine concentration was 4.8 ± 1.36 mg/dl. The patients underwent baseline and annual echocardiography, in addition to an electrocardiogram. Results: Most patients experienced a partial regression of left ventricular hypertrophy, and no congestive heart failure was documented. The mean hemoglobin level during rHuEPO therapy increased to 11.3 ± 1.2 g/dl, while the mean serum creatinine concentration did not change significantly. Conclusions: Our results confirm that early anemia correction in aged chronic renal failure patients permits improvement of the quality of life, of exercise performance, and of cognitive functions. Reduced transfusion need and regression of left ventricular hypertrophy favor a minor incidence of cardiac morbidity and contribute to reduce health costs.

Is zinc status a problem in the dietary treatment of chronic renal failure

Dr. P. Gilli, Divisione di Nefrologia, Arcispedale S. Anna, I-44100 Ferrara (Italy) Dear Sir, It is now generally accepted that dietary manipulations, such as reductions in protein and/or phosphate intake, can attenuate the progression of chronic renal insufficiency [1]. Thus, it is clear that more information is required to determine safe limits for protein restriction so as to avoid malnutrition. A particular problem could be represented by zinc deficiency, a common abnormality in proteinenergy malnutrition [2,3], which is also described in renal failure [3–5]. Zinc is an essential trace element, whose dietary availability is largely associated with animal protein intake. Its deficiency has been linked to many symptoms: skin lesions, reduced sexual function, taste and smell dysfunction, abnormal dark adaptation, impaired T-lym-phocyte function [4]. To evaluate zinc behavior in patients with renal failure, plasma zinc concentrations were determined by flame atomic spectroscopy in 46 patients (27 men, 19 women), aged 37–69 years (mean 50.9 ± 7.7), with different degrees of chronic renal failure (serum creatinine concentration from 1.6 to 10 mg%). Plasma zinc levels in patients with chronic renal failure (mean value 100.6 ± 20.5 μg%) were significantly different (p < 0.001) from those found in 63 hemodialysis patients (82.5 ± 14.6 μg%) and in 40 normal subjects living in the study area (112.0 ± 17.1 μg%). In the patients with different degrees of chronic renal failure, a statistically significant negative relationship was found between plasma zinc and serum creatinine concentrations (fig. 1). These data confirm that plasma zinc levels are reduced in patients with chronic renal failure and suggest that zinc deficiency may be related to the degree of renal insufficiency. Many factors could contribute to the decrease of plasma zinc levels in these patients. Not only does the use of aluminum hydroxide or cation exchange resins or supplements of inorganic ions [3] as well as the diminished enteral zinc absorption due to marked small bowel mucous membrane alterations [4] cause a decrease in plasma zinc levels, but the reduction in protein intake prescribed for renal failure patients does so as well.

The Determination of Plasma Transferrin Receptor as Good Index of Erythropoietic Activity in Renal Anemia and after Renal Transplantation

Both the plasma determinations of erythropoietic (EPO) and transferrin receptor (TfR) would provide a good characterization of anemia especially when mixed erythron disorders underlie, such as in renal failure. Immunologic assays of EPO and TfR, as well as standard hematologic determinations (hematocrit, reticulocyte count, serum iron, transferrin, ferritin) were performed in patients with chronic renal failure (CRF), in regular dialysis treatment (RDT) and in transplanted (TX) patients. In nonanemic TX patients both EPO and TfR ranged normally, whereas in anemic TX ones (Hct < 40%) both values were increased suggesting the physiologic response both of the kidney and of the erythron to decreased red cell mass. In transitory posttransplant erythrocytosis the increased values of TfR, with normal EPO values, would hypothesize a defective feedback to EPO release. Both EPO and TfR values were found increased in TX patients with adult polycystic kidney disease with persistent erythrocytosis (Hct > 50%), thus confirming previous observations. In CRF and RDT patients, all anemic, both EPO and TfR were normal, even though significantly low with respect to the degree of anemia. In RDT seriously anemic patients, the administration of recombinant human EPO induced different patterns of bone marrow response. We conclude that the determination of TfR would provide further information on renal anemia since the receptor increase mostly preceded the rise of Hct, evidencing those patients who will not have an effective bone marrow response to the therapy.

Acute Rhabdomyolysis and Hemoglobin Reduction after Bezafibrate Overdose in Hyperlipidemic Patients on Hemodialysis

Dr. Pier Luigi Bedani, Division of Nephrology, S. Anna Hospital, Corso Giovecca 203, I-44100 Ferrara (Italy) Dear Sir, Many patients with chronic renal failure (CRF) develop hyperlipidemia. Frequently, to correct this abnormality some form of pharmacological intervention is necessary. In clinical trials bezafibrate was administered to hyperlipidemic patients with CRF [1] or in regular dialytic treatment (RDT) [2]. Severe adverse reactions were reported infrequently but in some patients suffering from CRF [3] bezafibrate therapy induced rhabdomyolysis. We present 2 cases of bezafibrate overdose complicated with rhabdomyolysis and acute hemoglobin reduction in patients on RDT. Case 1: A 63-year-old man on RDT for 5 months owing to diabetic nephropathy was treated with bezafibrate at the dosage of 400 mg every second day. Four weeks later he experienced diffuse muscle weakness and nocturnal cramps. Laboratory studies showed a slight increase in serum creatine phosphokinase (CPK) and lactic dehydroge-nase (LDH) with a small reduction in Hb concentration (from 8.1 to 7.4 g/dl). Because of the persistence of hypertriglyceridemia, we recommended that the patient continue the bezafibrate therapy with a more appropriate dosage (i.e. 200 mg every third day). The erroneous understanding of our prescription made the patient carry on with the same dosage of the drug. After a further 4 weeks he experienced aching of his muscles, which gradually worsened, leading to generalized weakness and severe fatigue in walking. The most significant laboratory data are shown in figure 1. There was also a light increase of serum and urine concentrations of myoglobin without reduction of daily diuresis. The drug

Atrial Natriuretic Peptide and Urinary Sodium Balance during Physical Exercise

Atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma aldosterone and urinary fractional excretion of sodium (%FENa) were measured in 22 athletes before and after 1 h running. After exercise the hormones increased significantly, while %FENa decreased. In fact, the percent PRA increases resulted higher than the percent ANP increases with a significant inverse correlation. It is concluded that hemodynamic changes during strenuous and prolonged physical exercise lead to the inhibition of the natriuretic properties of ANP by stimulating the renin-angiotensin-aldosterone system, although a feedback mechanism of modulation between ANP and PRA seems to occur.