Evaluation of exercise testing for subjects with isolated proteinuria and/or hematuria of unclear significance.

BACKGROUND: A frequent problem that family doctors face is the meaning of small quantities of blood or protein in urine samples. Patients with this problem are often either neglected or referred to specialists for complex, expensive, and often invasive diagnostic procedures. Exercise testing has never been considered in nephrology, except for some attempts in diabetic patients. METHODS: We report on a study conducted over 12 years with patients referred for slight hematuria and/or proteinuria to determine whether exercise testing could be a diagnostic aid in some or all of them. We performed exercise testing using a treadmill preceded and followed by urine analysis, with a kidney biopsy within 10 days. Of the 94 patients enrolled in the study, only those with a positive exercise test turned out to have parenchymal nephropathy. At the end of the study, we simplified the quantification of exertion, dispensing with the treadmill and drastically reducing the number of urinary parameters considered. RESULTS: In patients with histological evidence of kidney damage, most of the variables increased significantly after the test. Statistical analysis also showed that determination of proteinuria and hematuria alone guaranteed maximum predictability. We found that it is also possible to simplify the quantification of effort/exertion and to drastically reduce the number of urinary parameters and still obtain significant results. CONCLUSIONS: Exercise testing provides useful information about the significance of microhematuria and proteinuria, reducing the number of cases that need to be referred to specialists. The method needs to be validated in other studies, but our results suggest that family doctors could use simple dipsticks to screen the many cases of microhematuria or proteinuria observed in daily practice. The method seems useful in eliminating doubts and unnecessary diagnostic costs.

The self-locating catheter: review and cost analysis.

The self-locating catheter invented by Nicola Di Paolo has been increasingly used in Italy and elsewhere since 1994, with about a thousand patients currently implanted every year. Twelve grams of tungsten inserted in the tip of the conventional Tenckhoff catheter during extrusion do not significantly change its form, but suffice to keep the tip firmly in the Douglas cavity. The validity of the new catheter is confirmed by a multicentric controlled study in a large population of peritoneal dialysis patients. This trial showed that patients with the new catheter have fewer episodes of peritonitis, tunnel infection, cuff extrusion, catheter malfunction, obstruction and leakage. This paper outlines the present situation and reports a comparative analysis of the costs of Tenckhoff and self-locating catheters.

Theoretical morphological approach to simple peritoneal sclerosis.

The term peritoneal sclerosis can be applied to a vast range of peritoneal alterations. At one end of the range we have the slight peritoneal sclerosis constantly associated with peritoneal dialysis, which may be defined as simple sclerosis. Its clinical impact is slight. The role of glucose in determining peritoneal sclerosis is supported by morphological studies and therefore backed by much biochemical and immunological data.

A mathematical approach to the evaluation of sediment transport capacity in the human urinary tract.

BACKGROUND: It is not yet clear whether forced diuresis is useful for flushing out of the urinary tract, especially in cases of renal calculi or infections. A series of experiments conducted initially in vitro and then in vivo in rabbits, using sand and small glass spheres, showed that sediments can be eliminated from the urinary tract by forced diuresis. When distilled water was used, the effect was greater, both as weight of sand and as number of spheres eliminated, than when normal saline was used. The different characteristics of the two liquids gave rise to different intrapelvic pressures for a given flow. MATERIALS AND METHODS: Intrapelvic pressures, and liquid and solid discharges in vitro and in rabbits were used in a fluid mechanics analysis of the phenomenon to obtain non-dimensional formulae so that the results in rabbits could be extended to humans. RESULTS: The results made it possible to evaluate solid transport capacity induced in a healthy human of given weight by drinking a given quantity of water in an hour. CONCLUSIONS: The mathematical model makes it possible to determine the quantity of water a patient must drink to induce a transport force sufficient for urinary tract wash-out.

Simple peritoneal sclerosis and sclerosing peritonitis: related or distinct entities?

AIM: The etiopathogenesis of sclerosing peritonitis is still debated, with some sustaining that it is a rare form of progression of simple peritoneal sclerosis and others that it is a primitive form. The aim of the present research was to clarify this question. MATERIAL AND METHODS: 438 peritoneal biopsies from 253 patients were re-examined. 174 were obtained prior to peritoneal dialysis and 224 after various periods of dialysis. Forty biopsies were from peritoneal dialysis patients who developed sclerosing peritonitis. Peritoneal morphology was studied for signs of transition from simple sclerosis to sclerosing peritonitis. RESULTS: Evidence was found sustaining the hypothesis that simple sclerosis to sclerosing peritonitis patients have distinct pathologies. CONCLUSIONS: The results confirm previous observations, excluding the existence of any type of relation between simple peritoneal sclerosis to sclerosing peritonitis.

Experimental evaluation of transport force in the rabbit ureter.

BACKGROUND: Cleaning the urinary tract by so-called 'wash-out effect' and promoting high diuresis has long been advocated but has had very little scientific backing and few prospective studies in international journals. AIM: To verify whether the physical laws describing the transport force of water in rivers and pipes are also valid for urinary outflow. METHODS: A laboratory model for measuring transport force, given liquid and solid capacity, was adapted to create an in vivo model based on the rabbit urinary tract. RESULTS: Fluid flow in the rabbit renal pelvis and ureters was found similar to flow in pipes, obeying the physical laws of water transport to some extent. When the quantity of liquid flowing in the urinary tract in unit time was doubled, the transport force increased by various orders of magnitude. When the liquid increased by a larger factor, the transport force became enormous. CONCLUSIONS: The results confirm the utility of maintaining high diuresis in patients with renal calculus, but stress the utility of drinking 1-2 liters of hypotonic water in a short time to obtain an enormous increase in transport force which increases the probability of a cleansing effect.

Prevention of peritoneal sclerosis: a new proposal to substitute glucose with carnitine dialysis solution (biocompatibility testing in vitro and in rabbits).

AIM: Commercial glucose peritoneal dialysis solutions expose the peritoneum to hyperosmolar glucose containing variable amounts of non-enzymic breakdown products of glucose. These solutions are toxic for the peritoneum. The aim of the present study is to compare in vitro and in vivo characteristics of a new dialysis solution containing carnitine, a naturally occurring compound, as substitute of glucose. MATERIAL AND METHODS: We compared in vitro and in the rabbit a new peritoneal dialysis solution containing carnitine, with two standard bicarbonate glucose peritoneal dialysis solutions and a solution containing icodextrin. RESULTS: In vitro and in vivo the solution containing carnitine seems to be more biocompatible than standard glucose solutions and those containing icodextrin. CONCLUSIONS: In our study the peritoneal dialysis solution containing carnitine seems to prevent the mesothelial changes observed with solutions containing glucose. Since carnitine has been extensively studied and seems to be well tolerated by hemodialysis patients, even at high doses for long periods, clinical trials in humans may be planned in the near future.

Extracorporeal blood oxygenation and ozonation (EBOO): a controlled trial in patients with peripheral artery disease.

BACKGROUND: Since 1990 our group has been using extracorporeal circulation to ozonate blood by an original method, known as extracorporeal blood oxygenation and ozonation (EBOO), with the aim of amplifying the results observed with ozone autohemotherapy. OBJECTIVE: To verify the hypothesis that EBOO improves the skin lesions typical of peripheral artery disease (PAD) patients. METHODS: Twenty-eight patients with PAD were randomized to receive EBOO or intravenous prostacyclin in a controlled clinical trial. The primary efficacy parameters were regression of skin lesions and pain,and improvement in quality of life and vascularisation. RESULTS: Patients treated with EBOO showed highly significant regression of skin lesions with respect to patients treated with prostacyclin. Other parameters that were significantly different in the two groups of patients were pain,pruritus, heavy legs and well-being. No significant differences in vascularisation of the lower limbs before and after treatment were found in either group. No side effects or complications were recorded during the 210 EBOO treatments. CONCLUSION: EBOO was much more effective than prostacyclin for treating skin lesions in PAD patients and also had a positive effect on patient general condition without any apparent change in arterial circulation. This suggests other mechanisms of action of EBOO.

Biocompatibility of a peritoneal dialysis solution with amino acids: histological evaluation in the rabbit.

OBJECTIVE: To determine the biocompatibility of a peritoneal dialysis (PD) solution containing amino acids compared to PD solutions containing glucose. DESIGN: The biocompatibility of three dialysis solutions containing 1.1% amino acids, 1.36% glucose, and 3.86% glucose, respectively, was evaluated in vivo in rabbits. METHODS: After 60 days of PD, peritoneal histological changes in rabbits were investigated by light and transmission electron microscopy. The parameters investigated were: (1) mesothelial damage; (2) submesothelial edema; (3) submesothelial cell infiltration; (4) submesothelial fibrosis; and (5) vascular alterations. Semiquantitative evaluations were performed for all the above alterations; quantitative morphometric evaluation was performed for mesothelial damage (cubic transformation of the mesothelium, areas devoid of mesothelium, submesothelial edema) and thickness of peritoneal arteriole walls. RESULTS: (1) Mesothelial damage was practically nonexistent in rabbits dialyzed with the solution containing amino acids, and intermediate and severe with low-glucose and high-glucose solutions, respectively. Both controls and rabbits dialyzed with amino acid solution showed flat continuous mesothelium; rabbits dialyzed with low-glucose solution showed cubic continuous mesothelium; and rabbits dialyzed with high-glucose solution showed cubic discontinuous mesothelium. Cytopathic mesothelial effects were slight with the solution containing amino acids and severe with both the low- and high-glucose solutions. Duplication and thickening of mesothelial basement membrane were never observed. (2) Submesothelial edema showed a worsening trend from controls to rabbits dialyzed with solution containing amino acids, low glucose, and high glucose. (3) No difference in submesothelial infiltration was found between groups. (4) Submesothelial fibrosis was never observed. (5) Vascular alterations were never observed. CONCLUSION: These results are evidence that PD solution with amino acids is more biocompatible than high- and also low-glucose solutions.

Necrotizing fasciitis successfully treated with extracorporeal blood oxygenation and ozonization (EBOO).

A case of necrotizing fasciitis in a dialysis patient is described. Since traditional therapies were unsuccessful, extracorporeal blood oxygenation and ozonation (EBOO) was tried. This technique is no longer in the experimental stage and is used routinely in our hospital. Patient condition improved radically after EBOO.

Accidental death due to erroneous intravenous infusion of hypertonic saline solution for hemodialysis.

The case of a continuous hemodialysis patient who died shortly after erroneous infusion with undiluted hypertonic solution is reported. Autopsy showed small parenchymal hemorrhages in all organs. Although producers take measures to prevent such errors by hospital staff, further steps are suggested for types of dialysis requiring reinfusion of large quantities of reinfusion hemodialysis solution.

Implant of autologous mesothelial cells in animals and a peritoneal dialysis patient.

Success in culturing human and animal peritoneal mesothelial cells for the purpose of study, led us to determine whether these cells could be autoimplanted in animals and man during peritoneal dialysis in cases of acute and extensive loss of mesothelial surface area. Using an original biopsy technique, we were able to cultivate and characterize from the structural and caryological point of view, human and rabbit peritoneal mesothelial cells. Staphylococcal peritonitis was provoked in 12 rabbits with in-dwelling peritoneal catheters and after 4 days of antibiotic therapy, 6 of them were autoimplanted with cultured mesothelial cells. In the animals sacrificed on the third and sixth days, direct morphological observation and autoradiographic techniques showed that the transplanted cells had taken and revealed a different picture from that in the non-transplanted rabbits. In a 56 year old female diabetic patient, upon insertion of the first peritoneal catheter, a specimen of mesothelial cells was cultured and then frozen. Seven months later after an episode of peritonitis from candida which dictated removal of the peritoneal catheter, since there was a sufficient number of cultured mesothelial cells and the patient consented, the implant was performed. Peritoneal biopsy by laparoscopy three and six days later showed that the cells had taken. The purpose of the study was merely to show that autoimplant of mesothelium in man and animals is possible.

[Alkaptonuria with ochronosis and monoclonal gammopathy]. / Alcaptonuria con ocronosi e gammopatia monoclonale

A case of alkaptonuria with ochronosis is described. It is suggested that such cases are not so much rare as unobserved. Their aetiology is to be sought in a metabolic error, though the pathogenesis is not clear. The syndrome is of interest because ochronosis, wich is the articular manifestation, is one of the few rheumatological affections with a certain aetiology. The case described is unusual on account of the presence of monoclonal gammopathy. Since the presence of myeloma and macroglobulinaemia could be excluded, an immunological relation was sought between the alkaptonuria and the particular serological picture.

Extracorporeal blood oxygenation and ozonation: clinical and biological implications of ozone therapy.

Some lines of evidence have suggested that the challenge to antioxidants and biomolecules provoked by pro-oxidants such as ozone may be used to generate a controlled stress response of possible therapeutic relevance in some immune dysfunctions and chronic, degenerative conditions. Immune and endothelial cells have been proposed to be elective targets of the positive molecular effects of ozone and its derived species formed during blood ozonation. On the bases of these underlying principles and against often prejudicial scepticism and concerns about its toxicity, ozone has been used in autohemotherapy (AHT) for four decades with encouraging results. However, clinical application and validation of AHT have been so far largely insufficient. Latterly, a new and more effective therapeutic approach to ozone therapy has been established, namely extracorporeal blood oxygenation and ozonation (EBOO). This technique, first tested in vitro and then in vivo in sheep and humans (more than 1200 treatments performed in 82 patients), is performed with a high-efficiency apparatus that makes it possible to treat with a mixture of oxygen-ozone (0.5-1 microg/ml oxygen) in 1 h of extracorporeal circulation up to 4800 ml of heparinized blood without technical or clinical problems, whereas only 250 ml of blood can be treated with ozone by AHT. The EBOO technique can be easily adapted for use in hemodialysis also. The standard therapeutic cycle lasts for 7 weeks in which 14 treatment sessions of 1 h are performed. After a session of EBOO, the interaction of ozone with blood components results in 4-5-fold increased levels of thiobarbituric acid reactants and a proportional decrease in plasma protein thiols without any appreciable erythrocyte haemolysis. On the basis of preliminary in vitro evidence, these simple laboratory parameters may represent a useful complement in the routine monitoring of biological compliance to the treatment. The clinical experience gained so far confirms the great therapeutic potential of EBOO in patients with severe peripheral arterial disease, coronary disease, cholesterol embolism, severe dyslipidemia, Madelung disease, and sudden deafness of vascular origin. Extensive investigation on oxidative stress biomarkers and clinical trials are under way to validate this new technique further.

Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) serum levels in patients on chronic hemodialysis.

The mechanisms underlying the skeletal resistance to PTH in patients on chronic hemodialysis (CHD) are not yet fully clarified. Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) modulate the genesis and activity of osteoclasts, however their role in renal osteodystrophy pathogenesis has not been clarified so far. The present study aimed to evaluate OPG and RANK-L serum levels in hemodialysis patients and whether OPG/RANK-L system could have a role in the skeletal resistance to PTH. In fasting blood samples obtained from 60 patients (36 males and 24 females) on CHD for at least 2 yr and from 40 healthy subjects of similar age and gender distribution as controls (CTRs), we measured serum OPG, RANK-L, bone alkaline phosphatase (B-ALP), N-terminal telopeptide of type I collagen (NTx), PTH(1-84), calcium and phosphate. In 30 of 60 hemodialysis patients, a blood sample was also drawn soon after the dialytic session. Serum levels of RANK-L, but not OPG, showed a slight but significant (p<0.05) decrease after the dialytic session. OPG resulted being about six times higher in CHD patients than in CTRs (38.7 +/- 16.2 vs 6.3 +/- 0.17 pg/ml), whereas RAN K-L serum levels were only slightly increased with respect to controls (0.88 +/- 0.47 vs 0.64 +/- 0.38 pmol/l). CHD patients showed serum PTH(1-84) and bone turnover higher than in CTRs. No correlation was found between OPG/RANK-L system and PTH or bone turnover markers. Instead, in the patients with high osteoclast activity (no.=21) OPG/RANK-L ratio was correlated (r=-0.41, p<0.01) with NTx serum levels, whereas in patients with decreased osteoclast activity (no.=39) no relationship was found. In conclusion, our findings showed that, although both OPG and RANK-L are accumulated in hemodialysis patients, only RANK-L and the balance between OPG and RANK-L seem to be related to osteoclast activity.