Cost analysis of dialysis modalities in Italy.

This study analyses management and costs of dialysis in the Italian National Health Service (NHS). Information on efficacy and health-related quality of life (HRQOL) based on the existing literature also is presented. The clinical differences between the dialysis modalities seem to be related to their appropriateness to specific patient groups. Efficacy rates are similar and the only differences are in complications and HRQOL. Traditional haemodialysis (THD) can be done by Italian patients in dialysis centres or in hospital. Highflux haemodialysis (HFHD) is generally only done in hospital. Peritoneal dialysis (PD) is usually done at home. The cost analysis was performed on a sample of Italian dialysis centres and hospitals, according to the full cost method. As expected, HFHD was more expensive than THD and PD, but no marked differences emerged among the different HFHD modalities. THD modalities in dialysis centres were less costly than in hospitals. Automated PD (APD) was much more expensive (almost twice) than continuous ambulatory PD (CAPD), the cheapest method in absolute terms. This study confirms that dialysis is costly and that it is very difficult to assess the cost-effectiveness of the different approaches. Although this study has limits, it should provide sufficient analytical information to local healthcare managers for more rational allocation of financial resources to dialysis services.

Individualized anticoagulation with dermatan sulphate for haemodialysis in chronic renal failure.

BACKGROUND: Dermatan sulphate (DS) is a selective thrombin inhibitor with antithrombotic properties and low bleeding potential. In preliminary studies it was reported to be effective for preventing clot formation in the haemodialysis circuit. METHODS: Ten patients on maintenance haemodialysis for chronic renal failure underwent three consecutive investigation phases. In phase 1 (individual dose titration), repeated dialyses were performed with increasing doses of DS until successful dialysis was obtained in two sessions at the same dose. In phase 2, individualized DS doses were validated by a randomized crossover comparison with the individual heparin dose of each patient. In phase 3, each patient underwent 24 consecutive dialyses with DS over 8 weeks. Successful dialysis was defined as completion of the procedure without visible clot formation in the bubble traps and lines or a greater than 20% decrease in dialyser capacity. Dialysis efficiency (decrease in serum urea and creatinine, Kt/V), APTT prolongation, bleeding time, and DS plasma concentrations were also assessed. RESULTS: Phase 1: successful dialysis was achieved in nine patients with 4 mg/kg DS as a predialysis intravenous bolus followed by continuous infusion of 0.65 mg/kg/h. One patient required 5 mg/kg plus 1.3 mg/kg/h. Phase 2: no statistically significant differences were found between DS and heparin in any of the investigated variables. Residual dialyser capacity and dialysis efficiency indexes indicated equivalent efficacy. Phase 3: residual dialyser capacity and dialysis efficiency did not change with time. There was no accumulation of DS in plasma. No bleeding or thrombocytopenia were observed. CONCLUSIONS: The dose of DS can be individually titrated to suppress clot formation during haemodialysis as efficiently as with individualized heparin. Such an individualized DS regimen maintains its anticoagulant efficacy and is safe in prolonged use.

Nitrendipine and enalapril improve albuminuria and glomerular filtration rate in non-insulin dependent diabetes.

The effects of 3, 15, and 27 months of treatment with nitrendipine (10 to 40 mg/day) and enalapril (5 to 20 mg/day) on diastolic blood pressure (DBP), overnight urinary albumin excretion (UAE) rate, glomerular filtration rate (GFR), and renal plasma flow (RPF) were studied prospectively in a parallel group design in 13 microalbuminuric non-insulin dependent diabetic patients with mild hypertension and biopsy-proven diabetic glomerulopathy. Throughout the study period DBP decreased in both groups to < 95 mm Hg. At three months UAE, GFR, and RPF did not change significantly. At 15 and 27 months UAE (microgram/min, geometric mean and 95% C.I.) decreased respectively from 47.4 (23.4 to 95.9) to 28.6 (10.3 to 79.4), and to 22.3 (10.9 to 45.2; P = 0.0005) with nitrendipine, and from 58.3 (30.3 to 110.9) to 44.1 (22.9 to 84.8), and to 14.7 (4.4 to 49.3; P = 0.0025) with enalapril. Four patients in each group were normoalbuminuric at 27 months and none became macroalbuminuric. At 15 months the GFR (ml/min/1.73 m2, mean +/- SD) increased from 69.5 +/- 15.2 to 96.6 +/- 22.0 (P < 0.05) with nitrendipine and from 58.9 +/- 10.7 to 78.5 +/- 11.0 (P < 0.05) with enalapril. At 27 months the GFR was still numerically higher that at baseline either with nitrandipine (81.2 +/- 7.8) and with enalapril (79.9 +/- 17.7) (P = 0.7). The RPF (ml/min/1.73 m2, mean +/- SD) at baseline and at 27 months was comparable either with nitrendipine (456.6 +/- 165.3 vs. 400.9 +/- 112.9) and with enalapril (400.3 +/- 81.3 vs. 399.0 +/- 123.7). Both treatments were well tolerated. This is the first evidence that long-term effective control of arterial blood pressure by a calcium channel blocker or by an angiotensin converting enzyme inhibitor, in addition to reducing albuminuria, also improves GFR in incipient nephropathy.

Long-term treatment with either enalapril or nitrendipine stabilizes albuminuria and increases glomerular filtration rate in non-insulin-dependent diabetic patients.

The effect of short- (98 days) and long-term (1 year) treatment with nitrendipine (10 to 40 mg/d) and enalapril (5 to 20 mg/d) on kidney function was studied prospectively in a parallel group design in 16 microalbuminuric non-insulin-dependent diabetic patients with mild hypertension and biopsy-proven diabetic glomerulopathy. At the end of the short-term treatment period diastolic blood pressure significantly decreased from 95.4 +/- 2.5 mm Hg to 83.5 +/- 3.5 mm Hg (P < 0.001) in the nitrendipine group and from 96.7 +/- 2.5 to 86.7 +/- 5.6 mm Hg (P < 0.001) in the enalapril group. Both overnight urinary albumin excretion rate and albumin fractional clearance tended to increase in the nitrendipine group and to decrease in the enalapril group, whereas the glomerular filtration rate and the renal plasma flow were similar to baseline in both study groups. At the end of the long-term treatment period diastolic blood pressure significantly decreased from 95.4 +/- 2.5 mm Hg to 86.0 +/- 6 mm Hg (P < 0.005) in the nitrendipine group and from 96.7 +/- 2.1 to 90.8 +/- 4.3 mm Hg (P < 0.05) in the enalapril group. Overnight urinary albumin excretion and albumin fractional clearance were similar to baseline in both study groups. The glomerular filtration rate significantly increased from 70.2 +/- 14.2 to 96.8 +/- 20.4 (P < 0.05) in the nitrendipine group and from 58.9 +/- 10.7 to 78.5 +/- 11.0 (P < 0.05) in the enalapril group. The renal plasma flow also significantly increased from 456.6 +/- 165.3 to 597.2 +/- 178.9 (P < 0.01) in the nitrendipine group.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognosis of untreated patients with idiopathic membranous nephropathy.

BACKGROUND: Defining the most appropriate treatment for patients with idiopathic membranous nephropathy is a matter of controversy. The course of the disorder is often benign, and the immunosuppressive regimens used in some patients have uncertain benefits and substantial risks. We studied the natural history of idiopathic membranous nephropathy in patients who received only symptomatic therapy. METHODS: We prospectively studied 100 consecutive patients (68 men and 32 women; mean [+/- SD] age, 51 +/- 17 years) with biopsy-proved idiopathic membranous nephropathy. The patients received diuretic or antihypertensive drugs as needed, but no glucocorticoid or immunosuppressive drugs. We examined the patients and measured their urinary protein excretion and serum creatinine concentrations every 6 months for a mean of 52 months. RESULTS: Twenty-four (65 percent) of the 37 patients followed for at least five years had complete or partial remission of proteinuria; in 6 others (16 percent), end-stage renal disease developed, and they required dialysis. As calculated by the Kaplan-Meier method, the estimated probability (+/- the standard error of the estimate) of retaining adequate kidney function was 88 +/- 5 percent after five years and 73 +/- 7 percent after eight years. The prognosis was poorer in men and in patients over 50 years of age, but not in patients with the nephrotic syndrome, hypertension, or hypercholesterolemia. CONCLUSIONS: Most untreated patients with idiopathic membranous nephropathy maintain renal function for prolonged periods and are likely to have spontaneous remission. These results do not support the use of glucocorticoids and immunosuppressive drugs in patients with idiopathic membranous nephropathy.

Heterogeneous nature of renal lesions in type II diabetes.

The nature of renal damage in patients with type II diabetes remains unclear. This study was directed to evaluate pathologic changes in 52 patients affected by type II diabetes with overt clinical nephropathy by conventional and morphometric techniques. The duration of diabetes ranged from 6 to 384 months, urinary protein excretion ranged from 0.9 to 9.2 g/24 h, and serum creatinine ranged from 0.9 to 9 mg/dL. Specimens were examined semiquantitatively by light microscopy, immunofluorescence, and electron microscopy. Glomerular tuft cross-sectional area was measured by a versatile computer system. Pathologic examination revealed three distinct patterns arbitrarily defined as Classes 1, 2, and 3. Class 1 included 19 patients with typical changes of diabetic nephropathy characterized by a high score of glomerulosclerosis (mean score, 2.1), marked glomerular hypertrophy (23,632 microns2), and arteriolar hyalinosis (mean score, 2). There was a positive correlation between glomerulosclerosis and arteriolar hyalinosis scores (P < 0.05). Class 2 included 16 patients showing chronic and aspecific changes. As compared with Class 1 patients, these patients had less glomerulosclerosis (mean score, 1.3) and less arteriolar hyalinosis (mean score, 0.8) but more severe ischemic glomerular lesions (mean score, 1.4) and arteriosclerosis (mean score, 2). Class 3 included 17 patients showing glomerular disease superimposed on diabetic glomerulosclerosis. There were no differences in age, mean duration of diabetes, renal function, urinary protein excretion, and mean arterial pressure among the three classes of patients. This study indicates that renal lesions in patients with type II diabetes manifest in a quite heterogeneous fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Nature and extent of glomerular injury induced by cyclosporine in heart transplant patients.

We sought to clarify whether low-dose cyclosporine (5.0 +/- 2.2 mg/kg/day) given for more than two years to prevent cardiac graft rejection induced glomerular injury and to quantify the extent of the lesions. After renal hemodynamic studies, renal biopsy specimens were obtained from 10 patients on cyclosporine and analyzed by a novel morphometric technique consisting of a tridimensional reconstruction of the glomerular tuft. Autopsy kidney specimens from three patients with no clinical history of renal disease, and from four patients who died with dilatative cardiomyopathy served as controls. The glomerular filtration rate and renal plasma flow were significantly depressed below normal values in transplant recipients given cyclosporine, averaging 35 +/- 8 and 325 +/- 94 ml/min/1.73 m2, respectively. Conventional light microscopy of specimens from controls and from patients who died with dilatative cardiomyopathy did not reveal renal structural abnormalities. By contrast kidney specimens from cyclosporine-treated patients had obliterative arteriolopathy and ischemic-type changes, with thickening and wrinkling of glomerular capillary wall. Morphometrical analysis of 28 control glomeruli and 40 glomeruli from patients with dilatative cardiomyopathy showed glomerular capillary tuft volumes (VCT) ranging between 1.2 and 2.3 microns 3 x 10(-6), whereas of 102 glomeruli from cyclosporine-treated patients 42.1% had VCT lower than 1.2 microns 3 x 10(-6) and 24.4% VCT higher than 2.3 microns 3 x 10(-6).(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant human erythropoietin to correct uremic bleeding.

Recombinant human erythropoietin may improve hemostasis of uremic patients by correcting anemia. However, a complete correction of renal anemia carries the risk of hypertension, encephalopathy, thrombosis, and hyperkalemia. Our aim was to establish the minimum level of packed cell volume (PCV) achieved with recombinant human erythropoietin that corrects the prolonged bleeding time in uremia. Twenty patients with chronic renal failure, anemia, and very prolonged bleeding time (greater than or equal to 15 minutes) were randomly allocated to erythropoietin or no specific treatment. The initial dose of erythropoietin was 50 U/kg intravenously (IV) three times a week. Every 4 weeks, the dose was increased by 25 U/kg until a normalization of bleeding time was achieved. Erythropoietin at a dose ranging from 150 to 300 U/kg/wk induced an increase in PCV to a range of 27% to 32% in all patients but one, and normalized bleeding time in all patients. A significant negative correlation (r = 0.898, P less than 0.001) was found between PCV and bleeding time measurements. Erythropoietin also significantly (P less than 0.01) increased values for red blood cell (RBC) distribution width (basal, 11.3 +/- 0.6; 12 weeks, 13.1 +/- 1.3). Platelet count and platelet function parameters did not significantly change. In untreated patients, no changes were recorded in all the parameters considered. These results establish in a controlled fashion that erythropoietin shortens bleeding time of uremic patients and indicate that a partial correction of renal anemia is enough to normalize bleeding time.

Effect of dietary proteins and lipids in patients with membranous nephropathy and nephrotic syndrome.

Twenty-four patients with idiopathic membranous nephropathy, long-lasting nephrotic syndrome and serum creatinine less than 2 mg/dl ate sequentially, in a randomized cross-over design, a normal protein diet containing 1.1 +/- 0.3 g/kg/day of proteins and a low protein diet containing 0.7 +/- 0.1 g/kg/day of protein, each diet for a period of 3 months. Both diets were low in fat (less than 30% of total calories) and cholesterol (less than 200 mg/day) content and rich in polyunsaturated fatty acids and in linoleic acid (10% of energy). Random assignment to one of the two 3 month diet periods was done after a RUN-IN period of at least one month on the hypolipidic normal protein diet. Glomerular filtration rate (inulin clearance), 24 hour urinary protein loss and serum albumin concentration did not significantly differ at the end of the two diet periods, indicating that long-term restriction of protein intake does not modify GFR or urinary protein loss in nephrotic patients. Serum total and LDL-cholesterol and daily proteinuria were significantly lower at the end of both diet periods than at the beginning and at the end of the RUN-IN period. We suggest that these changes were a consequence of the manipulation of dietary fat intake.

Factors affecting plasma free fatty acids rise during hemodialysis.

We studied the mechanisms responsible for causing acute changes in plasma lipids during hemodialysis. Dialysis decreased plasma triglycerides to the same extent as when heparin was given without dialysis. Cholesterol increased in proportion to hemoconcentration. Plasma free fatty acids (FFA) levels were also increased, but more so than with heparin alone. Glucose and acetate did not play a role, nor did carnitine loss, and hemofiltration elicited similar effects. The rise in plasma FFA is therefore likely to be caused by other as yet unknown mechanism.

[Acute hepatonephritis in a subject occupationally exposed to chloroform]. / Epatonefrite acuta in soggetto professionalmente esposto a cloroformio.

We describe a case of acute hepatonephritis in a worker of a pharmaceutical factory, due to sporadic and short exposures to chloroform at levels even 70 times higher than its TLV.

Outbreak of non-A, non-B hepatitis in centre haemodialysis patients: a retrospective analysis.

We reviewed the medical records of 177 patients who at 31 December 1985 had been on dialysis treatment for at least one year. Fifty cases of non-A, non-B hepatitis were found: 33 in 70 patients dialysed at the centre and 17 in 107 outpatients (P less than 0.0001). The difference was not related to blood transfusions but to the high prevalence of non-A, non-B in hospital patients who had not been transfused. The time on dialysis before the onset of non-A, non-B hepatitis became gradually shorter, from an average of 82 months before 1980 to 5.7 months in the patients starting haemodialysis after 1983. At follow-up, 7% of patients had abnormal hepatic enzymes 5 years from the onset of acute illness. The epidemiology of non-A, non-B hepatitis in haemodialysis patients appears to be similar to that of hepatitis B. Apart from blood transfusions, contamination of hospital environmental surfaces seems to be the major route of transmission. Our results strongly support a preventive programme for non-A, non-B hepatitis similar to that for hepatitis B, and a separate section for any patient with suspected non-A, non-B hepatitis must be considered.

Are "routine" clinical and laboratory examinations of any help in the treatment of chronic hemodialysis patients?

The relevance of routine physical examinations, laboratory tests, and x-rays in guiding therapeutic decisions was investigated in 54 patients on hemodialysis. Patients were observed for 1 year, while recording all therapeutic interventions and tracing the procedures that had determined them. In no case did a variation in treatment follow the routine physical examination of a patient who was not symptomatic or already signaled for BP or dialytic problems by the hemodialysis nurses. A number of major therapeutic interventions were conversely necessary for acute illnesses that could not be foreseen during the routine physician-patient encounter. Of the many laboratory tests, only the determination of complete blood cell count, serum electrolytes, and calcium and phosphorus levels were frequently associated with therapeutic decisions. No intervention was directly related with x-ray bone examination. On the whole, a subgroup of 11 "high-risk" patients who required frequent and multiple therapeutic interventions was identified, the remaining 43 needing only rare and minor adjustments. It is concluded that routine physical examinations are probably useless in identifying and treating intercurrent problems of patients with chronic end-stage renal failure and that only very few hematochemical laboratory tests should be regularly performed. On the basis of a benefit/risk and benefit/cost examination, it is suggested that personally tailored follow-up schemes would probably be a more appropriate way of monitoring patients on maintenance hemodialysis.

Management of myeloma kidney: an anti-light-chain approach.

This report describes the course of 23 patients with multiple myeloma and severe renal failure treated with a combination of plasmapheresis, chemotherapy, and supportive measures. Eight of ten patients with acute renal failure (ARF) obtained recovery of renal function, and in five of them serum creatinine concentration returned to normal. The remaining two patients died before the effect of treatment could be evaluated. Eleven of 13 patients with chronic renal failure (CRF) had substantial, albeit incomplete, improvement in renal function. The extent of functional recovery appeared to depend on the type of renal lesions, probably related to the duration of exposure to light chains. The median survival of the whole series of patients was 9 months, and five patients lived longer than 3 years. No clear-cut difference in survival was found between the group with ARF and that with CRF, although the latter presented higher values of serum creatinine at the time of diagnosis and residual renal insufficiency after the completion of treatment. Moreover, no significantly different survival times were found when the group with complete recovery of renal function was compared to that with minor improvement. Thus, renal failure, with the availability of effective forms of treatment of uremia, did not play a major prognostic role in our series. In contrast, the response to chemotherapy appeared to be the outstanding factor conditioning the duration of survival in these patients.

Biofiltration: an effective and simple method to reduce dialysis time.

Biofiltration: an effective and simple method to reduce dialysis time. Six stable anuric patients, on maintenance hemodialysis, were treated for 10 weeks with a parallel flow 1 m2 cuprophan filter, for 20 weeks with a parallel flow 1.2 m2 polyacrylonitrile filter using the biofiltration (BF) technique and again 10 weeks with the cuprophan filter. Usual monitors were used, without automatic control of ultrafiltration. Biochemical and hematological profile, urea kinetic parameters, incidence of hypotensive episodes, body weight and blood pressure did not change throughout the study. We conclude that three hours of BF, at least for 20 weeks, are as effective and well tolerated as four hours standard hemodialysis and could be of value in reducing dialysis time, to permit better utilization of dialysis beds.

Conjugated estrogens for the management of bleeding associated with renal failure.

Bleeding is a major complication of uremia. Both cryoprecipitate and desmopressin effectively shorten the prolonged bleeding time and favorably influence clinical bleeding, but the former carries the risk of transmitting blood-borne infectious diseases, and both cryoprecipitate and desmopressin have a short duration of action. Preliminary evidence has suggested that estrogens may be useful, and we therefore performed a randomized, double-blind, crossover trial comparing the effect of conjugated estrogens with that of placebo on hemorrhagic tendencies and the bleeding time in six patients with uremia who were on maintenance hemodialysis. Five daily infusions of placebo or conjugated estrogens were administered at the beginning of one-month trial periods. Estrogen shortened the bleeding time in all six patients. The effect was detectable six hours after the first infusion, reached its maximum in all patients between days 5 and 7, and lasted for 14 days. By day 16 after the last infusion, the bleeding time had returned to base line in four of the six patients. No side effects were noted during or after estrogen infusion. Estrogens did not influence the circulating level of von Willebrand factor or change its multimeric structure. Moreover, the defective platelet aggregation and thromboxane formation observed in the patients were not corrected by estrogens. We conclude that conjugated estrogens are an adequate alternative to cryoprecipitate or desmopressin for the treatment of bleeding associated with renal failure, especially when a longer duration of action is needed and immediate onset of the effect is not essential. The mechanism of action of estrogens remains to be clarified.

Superimposed nephritis: a separate entity among glomerular diseases?

The concomitant occurrence of two glomerular diseases in the same patient was diagnosed in seven out of 105 patients undergoing renal biopsy for suspected glomerulopathy. The most frequently associated disease was a membranous type glomerulopathy. The follow-up was characterized by a rapid deterioration of renal function and two patients were required to start a chronic hemodialysis program soon after the diagnosis. It is suggested that the observed coexisting patterns of glomerular injury do not occur on the basis of chance alone and should be considered as a separate entity in glomerular pathology. In all cases, clinical and pathologic findings were strongly suggestive for two consecutive distinct pathologic processes, thus justifying the use of the term superimposed nephritis. It is reasonable to assume that the mechanisms responsible for glomerular damage and for the evolution of the disease in superimposed nephritis are different from those regulating the corresponding glomerulonephritis when occurring alone. The high prevalence of membranous pattern in superimposed nephritis indicates that pre-existing glomerular alterations might favor an immune reaction in the subepithelial space.

Moderate doses of aspirin and risk of bleeding in renal failure.

Uraemic patients have a bleeding tendency thought to be due to platelet functional abnormalities, but haemodialysis paradoxically exposes patients to the thrombotic complications of arteriovenous shunts. Possible treatments of the latter have been debated. The effect of 100 mg/m2 aspirin on haemostatic function was studied in 29 uraemic patients on chronic haemodialysis who had normal or only slightly prolonged bleeding times. Aspirin did not significantly affect bleeding time in healthy controls but prolonged it in uraemic patients. In 12 of the 29 uraemic patients, the bleeding time after aspirin was longer than 15 min. Aspirin completely abolished thromboxane A2 generation by both control and uraemic platelets, indicating that its effect in uraemic patients is not due to differential inhibition of platelet cyclo-oxygenase. Products of lipoxygenase enzyme and factor VIII von Willebrand factor did not seem to have a role. A careful risk-benefit evaluation is necessary before giving aspirin to uraemic patients on haemodialysis to prevent thrombosis of the arteriovenous shunt.