[Gadolinium for DSA in two patients with azotemia: Images of suitable quality and risk of acute renal failure]. / Angiografia con Gadolinio in due pazienti azotemici: la qualita' diagnostica ed il rischio d'insufficienza renale acuta.

BACKGROUND: Gadolinium is an alternative angiographic contrast agent in patients with impaired renal function and high risk for iodinated contrast adverse reaction. We report two cases of acute renal failure caused by gadolinium (0.6 and 0.9 mmol/kg of body weight) after the execution of digital subtraction angiography (DSA) to produce diagnostic-quality images in two elderly diabetic patients with pre-existing renal insufficiency. Both patients needed dialysis treatments for as long as a few weeks until their renal function improved. In our opinion, and according to the guidelines of European Society of Urogenital Radiology, gadolinium has not been assessed as less nephrotoxic than iodinated contrast agents. In fact, 1.8 to 4.8 g of iodine, equally attenuated with a relatively high dose (0.2 to 0.4 mmol) of a gadolinium chelate, is a low iodine dose and could hardly have any important nephrotoxic effects. CONCLUSIONS: The maximum dose of gadolinium-based contrast agents should never exceed 0.2 to 0.4 mmol/kg in azotemic patients who are undergoing DSA, even though these doses of gadolinium may not provide images of suitable quality for diagnosis and intervention.

[Local therapy with platelet-derived growth factors for chronic diabetic ulcers in haemodialysis patients]. / Terapia locale con fattori di crescita piastrinici nelle ulcere croniche diabetiche in emodializzati.

BACKGROUND: The increasing number of diabetic patients who need dialysis treatment is the cause for the growing interest of nephrologists in ulcers of the lower limbs. It has been reported that platelet-derived growth factors, such as PDGF and TGF beta 1, are able to heal skin lesions due to diabetes. Therefore, a platelet gel (PG) has been developed to locally treat foot ulcers with a limited number of applications (3+/-1.7). METHOLOGY AND PATIENTS: The PG is a mix of concentrated platelets and cryoprecipitate activated by batroxobin in the presence of calcium chloride (or gluconate) that must be applied to the wound for three days. The surgeon and the dermatologist should then plan successive treatments because the necrotic tissue needs to be removed. We treated a 62-year-old diabetic man, who has been under treatment with insulin since the age of 36 and has been dialysed for three years. His right lower leg was amputated and he developed a chronic left foot ulcer that resulted in many septic episodes. His ulcer recovered in two months after 8 PG applications. CONCLUSIONS: Conventional therapy is not successful in 15-20% of diabetic feet. Uraemia and malnutrition may represent important risk factors for foot ulcers in diabetic patients who need advanced technology to stimulate tissue repair. The use of platelet growth factor may ameliorate ulcer healing thus reducing disease-associated morbidity and lowering health care costs.

Novel splicing and missense mutations in autosomal dominant polycystic kidney disease 1 (PKD1) gene: expression of mutated genes.

Autosomal dominant polycystic kidney disease (ADPKD) is a common disorder mostly characterized by cyst formation in kidney tubules. The majority of ADPKD cases is caused by mutations in the PKD1 gene, but no prevalent mutation has been reported. By heteroduplex analysis of the 3' single-copy region of the gene, we have searched for mutations in subjects from 40 ADPKD families of Northern Italy. Seven novel polymorphisms and three novel disease-associated mutations (R3718Q, L3851P and IVS45+56del25) were identified. Both missense mutations are located in the major extracellular loop of polycystin-1. The 25 bp deletion inside intron 45 did not affect 5' and 3' consensus splicing sites, but caused a 56 nucleotide out of frame-deletion due to activation of a cryptic 3' splice site in exon 46. The mutated RNA should produce a truncated polycystin 1 at the G binding peptide in the intracellular C-terminal end of the protein. RT-PCR analysis showed that the disease-associated mutations were present in transcribed sequences. In particular, RNA analysis of BHK cells transfected with PKD1 genomic DNA, including the deleted intron, showed that no normal transcript is produced by the deleted gene. This intronic mutation, found in a large pedigree, seems to be associated with a prevalence of cerebrovascular disease.

Autosomal dominant polycystic kidney disease linked to PKD2 locus in a family with severe extrarenal manifestations.

We report a large three-generation autosomal dominant polycystic kidney disease family from Northern Italy found to be associated with the PKD2 locus. Hepatic involvement (liver cysts, fibrosis, cholelithiasis or jaundice), subarachnoidal hemorrhage (1 case) and esophageal diverticula (1 case) were present in affected individuals. Among the older members, the males (aged 54-61 years) had hepatic cysts or fibrosis and were on chronic hemodialysis, the females (aged 69 and 70 years) had hepatic cysts, hepatomegaly, mild fibrosis and a mild and moderate renal impairment, respectively. In this family, clinical findings do not differ substantially from those reported for PKD1.

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.

Prevention of hepatitis C virus in dialysis units.

To understand how to prevent the diffusion of hepatitis C virus (HCV) in dialysis units, 289 chronic dialysis patients treated in a renal department from the beginning of 1990 to June 30, 1993, were studied. Patients were screened monthly for alanine aminotransferase values and every 3 months for anti-HCV antibodies. At the beginning of the study the prevalence of anti-HCV antibodies was 24.7%. Two study groups were defined. In the first, anti-HCV-positive patients were treated on separate machines; in the second, 13 anti-HCV-positive and 13 negative patients shared the same machines. Patients in the study were treated with traditional dialysis, employing low-permeability membranes and disposable dialysate circuits on machines without an ultrafiltration control device. The 'universal precautions' were rigorously applied. The use of blood transfusions was markedly reduced. Although new patients starting dialysis treatment revealed a high frequency of HCV positivity (10.8%), the overall prevalence of HCV infection in the department did not increase during the follow-up period. Furthermore, no seroconversion was found in patients on dialysis treatment, not only in the section where anti-HCV-positive patients were treated on separate machines, but also in the section where anti-HCV-positive and anti-HCV-negative patients shared the same machines. The possibility of an intradialytic diffusion of HCV appeared to be very low and the treatment of infected patients on separate machines not strictly necessary.

Analysis of polycystic kidney disease with two new microsatellite markers.

Two (CA) microsatellite polymorphisms have been studied in 209 subjects from Northern Italy, members of 27 Polycystic Kidney Disease families. Polymorphic alleles were analyzed by using a labelled PCR. Results obtained show that these markers highly improve the presymptomatic diagnosis of the disease in subjects at risk. In addition, our findings suggest that a region with a high recombination frequency should exist between PKD1 and SM7.

Changes in human epithelial kidney cells induced by nordihydroguaiaretic acid in vitro.

Some chemical agents induce kidney cystic changes in vivo comparable to human multicystic kidney disease. The biochemical aspects of human tubular cells were analysed by in vitro culture in the presence of nordihydroguaiaretic acid (NDGA). The uptake of 3H-thymidine in cultured cells in the presence of NDGA was comparable with control cultures, while 3H-hydroxyproline incorporation produced elevated values. The results suggest that NDGA in vitro induces modifications which may be related only to the synthesis of basement membrane components.

Hematological indices of erythropoietin administration in athletes.

Recombinant human erythropoietin (EPO), commercially available since 1988, is thought to be used by athletes in aerobic sports for the purpose of increasing oxygen transport and aerobic power. In an attempt to identify EPO administration, we have studied the peripheral blood of 20 subjects practising sports at an amateur level. Automated cytometry was performed on the blood samples before and during 45 days of EPO treatment. The same hematological indices were determined for a control population that consisted of 240 elite athletes from various sports. As expected following EPO treatment, RBC, [Hb] and Hct increased significantly (increments of 8%, 6.3% and 11%, respectively). A significant increase in reticulocyte count was also observed. In addition, automated erythrocyte analysis showed a significant increase in cells with a volume > 120 fl and hemoglobin content (HC) < 28 pg (hypochromic macrocytes, or MacroHypo): 0.06 +/- 0.09% before EPO, 0.48 +/- 0.63% after EPO. The EPO-treated subjects differed from the control population having higher values for Hct, mean corpuscular volume (MCV), Macro and MacroHypo. To investigate the possibility of using such variations in blood parameters to identify EPO treatment, individual values for Hct, MCV, Macro and MacroHypo for treated subjects and controls were plotted. Using the percentages of MacroHypo, a cut-off value surpassed in approximately 50% of the treated subjects and in none of the controls was established.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased uptake of radio labelled white blood cells into abdomen of uremics on peritoneal dialysis.

Peritonitis and exit-site tunnel infection are frequent causes of CAPD drop out. We studied 9 patients, 8 treated by CAPD and 1 by IPD. These patients underwent sonographic and scintigraphic study of the abdomen. All scintigraphic examinations showed a visceral uptake. In two cases, sub-clinical bowel inflammation, demonstrated by scintigraphic study, preceded a gram negative peritonitis. The scintigraphic study with radiolabelled white blood cells may be useful in identifying chronic aseptic inflammations and some bowel and exit-site conditions which are possible risk factors in some cases of peritonitis.

Effects of the recombinant human erythropoietin (rHuEPO) administration on hematologic parameters, red cell creatine and 2,3-diphosphoglycerate contents, in patients affected by end-stage renal disease.

Twenty patients with renal failure and severe anemia (hemoglobin range 6.6-8.7 g/dl) on thrice-weekly maintenance hemodialysis were treated with recombinant human erythropoietin (rHuEPO). After three months of intravenous (iv) therapy the hemoglobin increase averaged 2 g/dl, and was steadily maintained even after two months of subcutaneous (sc) therapy. The significant increase of macrocyte counts, determined by an automated red blood cell counter after both steps of therapy, suggested the release of young red cells (large cells) into blood circulation. This assumption may be supported by the significant increase of the red cell creatine contents. 2,3-diphosphoglycerate (2,3-DPG) levels of the erythrocytes did not significantly change after rHuEPO administration.

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.

Non-A, non-B hepatitis and anti-HCV antibodies in dialysis patients.

To define the prevalence of non-A, non-B hepatitis, antibodies to HCV were detected in 193 patients on renal replacement therapy (52 transplant and 141 hemodialysis patients) and in 50 staff members of a Nephrology Department. Unequivocal seroconversion was documented in 5 transplant (9.6%) and in 26 dialysis patients (18.4%). In the dialysis population, the prevalence of anti-HCV antibodies was evaluated in patients grouped according to the number of blood transfusions and to the different sections of dialytic treatment. The most striking findings were the marked differences in the prevalence of anti-HCV antibodies among patients treated in different sections (from 0% to 70%), and the presence of a significant increase in alanine-amino-transferase (ALT) concentrations in 14 anti-HCV negative patients. The results suggest that the diffusion of non-A, non-B hepatitis is mainly transfusion-related, with the possibility of significant environmental diffusion related to the violation of infection-control measures. The current immunoassay is probably unable to detect the actual frequency of the infection.

Serum erythropoietin activity following kidney transplantation.

31 patients with successful kidney grafts were studied. Ep, Ht, Hb and T lymphocytes were determined. Native and grafted kidneys were studied by ultrasonography. After KT, 45% of patients had PTE and in 71% of these a spontaneous regression was observed. Mean serum Ep activity in patients with and without PTE was significantly higher than in healthy controls. Different erythroid colony growth sensibility and responsiveness to higher serum Ep (PTE and non-PTE patients) may be due to T3 cell interaction with BFU-E.

Serum erythropoietin in cross-country skiers.

Serum erythropoietin (Epo) activity, hemoglobin (Hb), and hematocrit (Ht) were determined in 21 cross-country skiers during the training season. The Epo levels were not significantly reduced in the skiers relative to the normal population (P less than 0.01 and P less than 0.001, respectively). In 11 athletes Epo, Ht, urinary gamma-glutamyltransferase, N-acetyl-beta-glucosaminidase, and microalbuminuria were determined before and after a 50-km ski race at 1600 m above sea level. A significant increase of these variables (except for Ht) was found after the competition (P less than 0.001). It is concluded that while the reductions in Hb and Ht, which are typical of several endurance exercises, are not accompanied by a renal hypoxia sufficient to stimulate Epo overproduction, the renal hypoxia reached during the strenuous exercise of the race at altitude may be effective in determining blood increases in Epo.