Conceptual basis and methodology of the SOPHIA study.

To clarify the role of gene polymorphisms on the effect of losartan and losartan plus hydrochlorothiazide on blood pressure (primary end point) and on cardiac, vascular and metabolic phenotypes (secondary end point) after 4, 8, 12, 16 and 48 weeks treatment, an Italian collaborative study - The Study of the Pharmacogenomics in Italian hypertensive patients treated with the Angiotensin receptor blocker losartan (SOPHIA) - on never-treated essential hypertensives (n = 800) was planned. After an 8 week run-in, losartan 50 mg once daily will be given and doubled to 100 mg at week +4 if blood pressure is more than 140/90 mmHg. Hydroclorothiazide 25 mg once daily at week +8 and amlodipine 5 mg at week +16 will be added if blood pressure is more than 140/90 mmHg. Cardiac mass (echocardiography), carotid intima-media thickness, 24 h ambulatory blood pressure, homeostatic model assessment (HOMA) index, microalbuminuria, plasma renin activity and aldosterone, endogenous lithium clearance, brain natriuretic peptide and losartan metabolites will be evaluated. Genes of the renin-angiotensin-aldosterone system, salt sensitivity, the beta-adrenergic system and losartan metabolism will be studied (Illumina custom arrays). A whole-genome scan will also be performed in half of the study cohort (1M array, Illumina 500 GX beadstation).

Use of antihypertensive and lipid-lowering drugs: the management of cardiovascular risk in clinical practice.

The objective of the study was to analyse the treatment of high blood pressure (BP) and hypercholesterolaemia, as well as the effect of individual or combined antihypertensive-hypocholesterolaemic therapy on BP control and on circulating cholesterol. A retrospective study was performed using clinical data recorded in the general practitioner's database. The sample included all patients, aged > or =18 years, with BP reading or low-density lipoprotein (LDL) cholesterol measurement recorded between January 2003 and December 2004. BP and LDL cholesterol targets were defined using cutoffs based on the guidelines of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7) and the National Cholesterol Education Program (NCEP/ATPIII). The study included 4764 patients (mean age 67.6+/-11.8 years, 43.5% males). Target BP was achieved in a higher number of patients under combined antihypertensive-hypocholesterolaemic therapy than in those treated only with antihypertensives: 57.0 vs 50.0% in patients with history of cardio/cerebrovascular (CV) hospitalization, 27.0 vs 16.9% in patients with diabetes or chronic renal insufficiency (CRI) and 59.7 vs 49.1% in patients with no CV hospitalization nor diabetes and nor CRI. The LDL cholesterol target was achieved in 61.3% of the subjects: it was independent on the therapy (individual or combined), but related to the degree of cardiovascular risk. Analysing the data contained in the general medicine database made it possible to evaluate the treatment of high BP and hypercholesterolaemia in relation to cardiovascular risk in clinical practice and to establish the need to pay greater attention to achieving the objective set by guidelines.

Colour-Doppler US evaluation of patients with hypertension and nephropathy.

PURPOSE: The objective of this study was to assess the utility of colour-Doppler ultrasound (CDUS) in the investigation of patients with hypertension and nephropathy and to determine the association between hemodynamically significant stenoses of the renal arteries and abdominal aorta aneurysms (AAA). MATERIALS AND METHODS: Between January 2000 and December 2004, 467 patients (205 women and 262 men, age range 20-96 years) with hypertension and chronic renal failure were referred to us for CDUS evaluation of renal morphology and haemodynamics and identification of haemodynamically significant stenoses of the renal arteries. RESULTS: Of the 467 patients examined by CDUS, 159 (34%) showed no signs of renal artery stenosis (RAS) or nephropathy and were therefore started on medical therapy. The remaining 308 (66%) exhibited signs of haemodynamically significant stenoses of the renal arteries or of nephropathy. AAA was identified in 19 of the 333 patients (5.7%) without haemodynamically significant renal artery stenoses and in 15 of the 134 patients (11.2%) with renal artery stenoses. CONCLUSIONS: Our results confirm the fundamental role of CDUS in the management of patients with suspected or known renovascular disease. The information provided by CDUS on renal hemodynamics is fundamental for a correct clinical approach.

Relationship between body weight, quality of life and cardiovascular risk factors: a general population based Italian experience.

BACKGROUND: Within the framework of the Progetto Faenza, the aim of this study was to evaluate the effect of cardiovascular risk factors (CVRF) on the health-related Quality of Life (H-rQoL) of a cohort of patients in the province of Ravenna, on the basis of body mass index (BMI). METHODS: The following data were collected for each subject: age, sex, weight, height, glycemia, cholesterol (total, HDL and LDL), creatinine, uricemia, systolic arterial pressure (SAP) and diastolic arterial pressure (DAP), presence/absence of previous CV disorders, arterial hypertension, diabetes, antihypertensive therapy, smoking habits and physical exercise. To evaluate the H-rQoL the SF-36 general health survey questionnaire was used, filled in by the patient at the first examination. To test the significance of the differences between the groups (divided by classes of Body Mass Index) as regards the metabolic indicators, a univariate analysis of variance was performed; on the other hand, to assess which factors affect H-rQoL a multivariate analysis was carried out, considering p<0.05 as significant. The results are expressed as +/- 1SD. RESULTS: Of the 1108 subjects enrolled in the study, 343 subjects (31.2%), including 154 males with a mean age of 44.9 +/- 14.9 years, filled in the SF-36 questionnaire. A BMI within the normal range corresponds to a more satisfactory metabolic (p<0.05) and QoL (p=0.001) picture. Age (p<0.001), presence of previous CV disorders (p=0.005), the use of antihypertensive drugs (p=0.041) and physical exercise (p=0.002) correlated significantly with H-rQoL values. CONCLUSIONS: Health condition and perception are significantly affected by a clinical situation characterized by excess weight.

Risk factors for uncontrolled hypertension in Italy.

To identify factors related to poor control of blood pressure in primary care, we designed a retrospective case-control analysis of clinical and demographic data recorded in the General Practitioners (GP) database. Study data were provided on a voluntary basis by 21 GPs from a practice-based network in primary care. The study included 2519 hypertensive patients enrolled between January 1 and December 31, 2000. The interventions were antihypertensive medication, and the main outcome measures were control of systolic and diastolic blood pressure (BP). The independent variables considered were: age of patient and GP; patient gender, body mass index, history of smoking, diabetes mellitus, or cholesterol tests; family history of hypertension; previous visits for cardiologic, nephrologic, or vascular surgery evaluation; prior hospitalizations for myocardial infarction or heart failure, and number of admissions for surgery; length of patient follow-up, type of antihypertensive medication, mean daily dosage, adherence to the drug regimen, and number of other medications currently being taken by the patient. Blood pressure was uncontrolled (>140/90 mmHg) in 1525 (60%) of the 2519 hypertensive patients enrolled. The presence of diabetes mellitus, increasing patient age, and increasing GP age significantly increased the risk of uncontrolled BP. Factors significantly associated with a reduced risk of uncontrolled BP were the number of other medications currently being taken by the patient and a prior history of MI. We conclude that the failure of antihypertensive medication to adequately control BP is determined by both the patient's characteristics and factors related to the patient-doctor relationship. Successful treatment of hypertension requires patient adherence to the regimen that has been agreed on by the patient and the physician.

Pharmacoutilization and costs of osteoarthritis: changes induced by the introduction of a cyclooxygenase-2 inhibitor into clinical practice.

OBJECTIVE: To establish whether the introduction of a cyclooxygenase-2 inhibitor has led to changes in pharmacoutilization in the treatment of osteoarthritis (OA) in clinical practice. METHODS: Administrative and general practice databases were cross-linked to analyse the use of non-steroidal anti-inflammatory drugs (NSAIDs) and gastroprotective agents (GPAs) before and after the introduction of rofecoxib. Costs of treatment and costs of hospitalization for gastrointestinal events were also considered. RESULTS: A total of 3090 patients were evaluated. A significant reduction in the use of GPAs in the rofecoxib group was observed, corresponding to reductions of 64 and 59.7% compared to NSAIDs among patients in incident and prevalent cases respectively. The weighted mean daily cost of therapy with rofecoxib in incident cases was 1.88 euro, 7.4% lower than that of NSAIDs (2.03), and in prevalent cases it was 1.87 euro, 28.1% higher than that of NSAIDs (1.46). Although the rate of hospitalization was similar, there was an additional daily cost per patient of 186.6 for patients being treated with NSAIDs and 21.6 euro for those being treated with rofecoxib. CONCLUSIONS: The cyclooxygenase-2 inhibitor rofecoxib determined substantial changes in the pharmacoutilization and costs of OA.

Long-term persistence with antihypertensive drugs in new patients.

The objective of this study was to investigate stay-on-therapy patterns over 3 years among patients prescribed different classes of antihypertensive drugs for the first time. A retrospective analysis of information recorded in the drugs database of the Local Health Unit of Ravenna (Italy) was carried out on 7312 subjects receiving a first prescription for diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II antagonists between 1 January and 31 December 1997. Patients were followed up for 3 years. All prescriptions of antihypertensive drugs filled during the follow-up periods were considered. The patients continuing or discontinuing the initial treatment, the duration of treatment, and the doses taken were all calculated, as well as main factors influencing the persistence rate. The drugs prescribed were predominantly ACE-inhibitors, followed by calcium channel blockers, diuretics, beta-blockers and angiotensin II antagonists. A total of 57.9% of patients continued their initial treatment during the 3-year follow-up period, 34.5% discontinued the treatment, whilst 7.6% were restarted on a treatment in the third year. Persistence with treatment was influenced by: age of patient (persistence rate increasing proportionately with advancing years), type of drug first prescribed (persistence rate higher with angiotensin II antagonists, progressively lower with ACE-inhibitors, beta-blockers, calcium channel blockers and diuretics), gender of patient (persistence was better in males), age of general practitioner (GP) (the younger the GP, the better the persistence rate) and gender of GP (better stay-on-therapy rate with male GP prescribing). In the case of patients treated continuously, mean daily dose increased progressively over the 3 years. With adequate markers, helpful data can be collected from prescription claims databases for the purpose of monitoring the persistence of patients in continuing their medication, and the quality of antihypertensive treatment in a general practice setting.

Effects of clinical and individual variables on quality of life in chronic renal failure patients.

BACKGROUND: The purpose of this study was to assess the effects of baseline characteristics of patients, chronic renal failure and its treatment on quality of life. METHODS: To investigate the health status we used a questionnaire, the SF-36, during individual interviews. The study involved i) a cross-sectional observational stage, lasting from 1 Sept. 1997 to 30 April 1999, on all the patients undergoing conservative treatment, hemodialysis, peritoneal dialysis and kidney transplantation in district of Ravenna, and ii) a longitudinal stage, when the subjects were administered two questionnaires at an interval of at least 16 months. The quality of life data collected during the cross-sectional stage were analyzed to establish any correlations between age, type of treatment of chronic renal failure and hemoglobin levels. Patients under dialysis were also examined for any interference caused by the center where dialysis was done. RESULTS: Multivariate analysis on the data collected during the cross-sectional stage showed that chronic renal failure treatment and age affected the quality of life scores for the following parameters: physical activity, bodily pain, general health and vitality (age was inversely related to the scores). Transplanted patients and those on conservative treatment enjoyed the best overall quality of life, followed by those on peritoneal dialysis and those on hemodialysis. The physical domain scores were strongly associated with age, hemoglobin and diabetes. Multivariate analysis of the longitudinal study indicated that the interval between the beginning and the end of the observation period, age and diabetes greatly influenced quality of life. CONCLUSIONS: The data confirmed that age and diabetes have a strong influence on the quality of life and that the long period of treatment, with the absence of any prospect of resolving the clinical situation, has a negative effect on the quality of life in uremic patients.

[Evaluation model of the effect of Rofecoxib on the co-prescription of gastroprotective agents observed during the treatment of osteoarthritis]. / Modello valutativo dell'effetto sulla co-prescrizione di gastroprotettori osservato durante il trattamento dell'artrosi con Rofecoxib.

OBJECTIVE: This study was conducted to define an evaluation model to estimate changes in the co-prescription of gastroprotective agents (GPAs) induced by rofecoxib in the treatment of osteoarthritis (OA). METHODS: On the basis of a cross-linking information, which were stored in different administrative and clinical databases, a multivariate regression analysis was used to develop the model. Data were collected by 30 general practitioners of the Local Health Unit of Ravenna (middle-north of Italy). RESULTS: The study population consisted of 2,944 patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) and 487 treated with rofecoxib. Patients treated with rofecoxib generally presented a higher number of gastrointestinal damage risk factors and also a lower level of GPAs co-prescription compared to those treated with NSAIDs. Including in the model variables such as type of anti-inflammatory treatment (NSAIDs or rofecoxib), gender, age by class, previous hospital admissions due to gastrointestinal complications, number of different NSAIDs used, and prescription of corticosteroids, the regression equation and its coefficients were identified. A non-linear relationship between the percentage of patients treated with rofecoxib and the relative reduction of GPAs co-prescription was found. It has been estimated the basis of the registered percentage of patients treated with rofecoxib (17,6%) adjusting for gastrointestinal damage risk factors, and on a 63% (CI95%: 55%-70%) relative reduction of GPA use with rofecoxib with respect to NSAIDs was estimated. CONCLUSIONS: Based on data collected in the clinical practice after the introduction of rofecoxib, a model evaluating the relationship between the frequency of its use in the OA population and the expected reduction of GPAs, has been developed.

Pharmacoutilization of antihypertensive drugs: a model of analysis.

OBJECTIVES: To identify clinical and economic indicators of pharmacoutilization of antihypertensive drugs. PATIENTS AND METHODS: 4614 subjects receiving a first prescription for amlodipine, atenolol, fosinopril, indapamide, or losartan were included in the study. All prescriptions filled during the study period from January 1, 1997 to December 31, 1998 were considered. A retrospective analysis was carried out on information recorded in the drug database. The percentage of patients continuing, discontinuing, and switching the initial treatment, duration of treatment, and doses used were calculated together with total costs. RESULTS: A large proportion of patients (65.1%) discontinued the treatment. From the analysis of the mean daily dose taken by patients who continued the treatment, it was found that many subjects took a drug dosage which was below the therapeutic dose range, whereas the administration of doses above the therapeutic range occurred only occasionally. Continuation of treatment accounted for 48.1% of total costs, switching accounted for 20.8%, and discontinuation represented 31.1% of total expenditures. CONCLUSIONS: With adequate markers, helpful data can be collected for monitoring the quality of antihypertensive drug prescriptions and the rational usage of resources in the general practice setting.

The PANDORA project: results of the cost of illness analysis.

AIMS: To evaluate the cost of illness from hypertension for the Italian National Health System (NHS). METHODS AND RESULTS: A prospective analysis was carried out on clinical and economic data recorded in the general practitioners' (GPs) database. Twenty-one GPs working in the Ravenna area in Italy took part in the project on a voluntary basis. The study included 1047 hypertensive patients enrolled between 1 June and 31 December 1997 and continued for 365 days from the date of enrolment. The following costs were calculated: antihypertensive drugs, laboratory tests and instrumental procedures, GP visits for blood pressure control, specialist visits, casualty visits, hospitalisation due to cardiovascular problems. In the whole sample, the most relevant cost is due to antihypertensive drugs (42.7%), followed by hospital admission (28.4%), GP visits (15.1%) and tests (10.6%). The total mean cost was significantly lower in incident (no previous treatment) than in prevalent patients (already treated) (457 512 vs 725 573 Italian Lira (ITL), P < 0.05) and in older rather than in younger patients (1171 410 vs 796 452 (ITL) P < 0.05). (In the text the equivalent is given in Euros, Pounds Sterling and US dollars). CONCLUSION: Our study should be considered as preliminary, nevertheless it could represent a step towards the evaluation of the true cost of hypertension.

The Pandora Project: results of the pilot study.

The Pandora Project was designed to develop a computer-assisted system to improve the appropriateness and effectiveness of hypertension treatment in clinical practice and to organize a database both for epidemiologic and economic assessments. The feasibility study was conducted by five general practitioners (GP) who enrolled 244 patients over a period of 6 months. The follow-up lasted 6 months. The computer system implemented provided a linkage among GP's office, hypertension unit, Ravenna Health Service databases, and a remote station. A total of 209 patients completed the follow-up period; 56% of patients were not normotensive despite the antihypertensive treatment. The prevalence of overweight, physical inactivity, and family history of high blood pressure and hypercholesterolemia was greater than 50%. Unplanned check-ups by GP occurred 9%. Six patients were admitted to the hospital eight times; 19 patients attended the casualty department 21 times. The mean total direct cost per patient was 567,800 Italian Lire (ITL) and increased to ITL 732,000 or to ITL 825,900 when lost productivity, calculated according to two different formulas, was added. This pilot study confirms the need and feasibility of implementing the Pandora Project in general practice in Ravenna.

Prevalence of hypertension in patients on peritoneal dialysis: results of an Italian multicentre study.

BACKGROUND: The tenet that peritoneal dialysis is capable of either normalizing or improving blood pressure control in uraemic patients is based on outdated or monocentric experiences. Therefore, we assessed the prevalence of hypertension and the efficacy of antihypertensive therapy in a large, multicentric cohort of patients on peritoneal dialysis. METHODS: Twenty seven out of the 50 centres belonging to the Italian Co-operative Peritoneal Dialysis Study Group took part in the study. The main patient selection criteria were: peritoneal dialysis therapy for at least 3 months and no peritonitis or changes in dialysis technique for at least 1 month. Clinical blood pressure was measured according to WHO/ISH guidelines. Ambulatory blood pressure monitoring was carried out using a SpaceLabs 90207 recorder. Hypertension was defined according to WHO/ISH criteria and staged according to the criteria of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC), 5th Report. Ambulatory blood pressure monitoring recordings were used to evaluate white-coat hypertension, blood pressure load and the dipping phenomenon. RESULTS: Five hundred and four subjects were evaluated. Hypertension was prevalent in 88.1% of the population, and 362 out of 444 hypertensive patients were on antihypertensive therapy. JNC staging revealed that 188 patients had moderate to severe hypertension. Blood pressure load was pathological in 77.3% of the patients receiving antihypertensive treatment. White-coat hypertension was identified in 9.1% of the hypertensive patients not on antihypertensive therapy, and 53.1% of the patients were non-dippers. CONCLUSIONS: The study demonstrates that hypertension is a dramatic, unsolved problem in uraemic patients treated with peritoneal dialysis, and casts doubts on the effectiveness of our current peritoneal dialysis strategies and pharmacological management of hypertension.

Myths and reality concerning hypertension in peritoneal dialysis patients: results of a multicenter study.

OBJECTIVES: To evaluate the prevalence of hypertension, the average blood pressure level, the 24 h blood pressure profile, and the efficacy of antihypertensive therapy for a large population of peritoneal dialysis patients.DESIGN: A cross-sectional, observational multicenter study. METHODS: From 504 peritoneal dialysis patients (18% of the Italian peritoneal dialysis population) involved in a multicenter observational study, we selected 414 who had undergone successful ambulatory blood pressure monitoring (i.e. no hours with data absent, >/= 75% successful readings and monitoring duration >/= 24 h). Office blood pressure measurements and ambulatory blood pressure monitoring were performed for each patient on the same day with a standard mercury sphygmomanometer and a SpaceLabs 90207 device, respectively.RESULTS: According to World Health Organization/International Society of Hypertension criteria, 44 peritoneal dialysis patients (10.6%) were normotensive and 370 patients (89.4%) were hypertensive, 304 (82.1%) of whom were being administered antihypertensive therapy. Daytime systolic and diastolic blood pressures were both significantly lower than office systolic and diastolic blood pressures (140.7 +/- 19.7/72.1 +/-11.1 versus 148.3 +/- 23.6/85.6 +/- 12 mmHg; P < 0.001). The difference between office blood pressure and daytime blood pressure was significantly correlated to office blood pressure (P < 0.001 for systolic and P < 0.001 for diastolic). The diurnal blood pressure rhythm evaluated by visual inspection of hourly mean plots was not influenced by sex, age, antihypertensive treatment, and peritoneal dialysis modality. Systolic and diastolic blood pressures exhibited a day-night mean decreases of 8.6 +/- 11.7 and 7.7 +/- 6.9 mmHg, respectively, and daytime blood pressure values were significantly higher than night-time ones (P < 0.001). Two hundred and twenty patients (53.1%) were nondippers according to O'Brien's criteria, 247 patients (59.7%) were nondippers according to Verdecchia's criteria, and 269 patients (65.0%) were nondippers according to Staessen's criteria. Only 39 patients (9.4%) had a reversed circadian rhythm. The day-night differences of systolic and diastolic blood pressures were in a unimodal distribution. Among hypertensive patients not being administered antihypertensive therapy, only six patients ( five women and one man) had white-coat hypertension. Among hypertensive patients being administered antihypertensive therapy, 235 patients (77.3%) had 24 h blood pressure loads > 30%.CONCLUSION: There is a high prevalence of hypertension among peritoneal dialysis patients. White-coat hypertension is very rare in this population. Despite the extensive use of antihypertensive therapy, control of blood pressure is maintained in a large number of our peritoneal dialysis patients. Any classification of patients into dipers and nondippers must be interpreted cautiously.

24-hour blood pressure control by once-daily administration of irbesartan assessed by ambulatory blood pressure monitoring. Irbesartan Multicenter Investigators' Group.

OBJECTIVES: To compare 24 h ambulatory blood pressure and trough office blood pressure lowerings after 8 weeks of therapy with 75 mg irbesartan once a day, 150 mg irbesartan once a day , and 75 mg irbesartan twice a day versus placebo; and to assess safety and tolerability of irbesartan therapy. DESIGN: Multicenter, double-blind, randomized, placebo-controlled trial. SETTING: Sixteen centers in Italy. PATIENTS: Caucasian patients (n = 215) aged > or = 18 years with seated diastolic blood pressure 95-110 mmHg and ambulatory diastolic blood pressure (ADBP) > or = 85 mmHg. PRIMARY OUTCOME: Mean 24 h ADBP after 8 weeks of irbesartan therapy. RESULTS: Mean changes (value before treatment minus value after treatment) in ADBP for placebo, 75 mg irbesartan once a day, 150 mg irbesartan once a day, and 75 mg irbesartan twice a day were -0.2, -5.4, -7.2, and -7.2 mmHg, respectively; respective changes in ambulatory systolic blood pressure were +1.6, -8.3, -10.5, and -9.7 mmHg. All irbesartan regimens reduced trough office seated diastolic blood pressure and seated systolic blood pressure after 2 and 8 weeks of treatment (all P < 0.01, versus placebo except for seated systolic blood pressure in patients in the 75 mg irbesartan once a day group). Trough: peak ratios were > or = 55% with 150 mg irbesartan once a day. Percentages of patients whose blood pressures were normalized with 150 mg irbesartan once a day (45%) and 75 mg irbesartan twice a day (47%) were greater than those with placebo (14%, P < 0.01) and with 75 mg irbesartan once a day (19%, NS, versus placebo). Adverse events with irbesartan were similar to those with placebo. CONCLUSIONS: All irbesartan regimens significantly reduced mean 24 h ADBP and ambulatory systolic blood pressure, and were well tolerated. Administration of 150 mg irbesartan once a day provided significant reduction of blood pressure for 24 h, equivalent to that obtained with the same daily dose divided into two separate administrations.

Sodium-lithium countertransport activity in red blood cells of patients with IgA nephropathy.

In this paper we report some results of our studies on patients with immunoglobulin (Ig)A nephropathy regarding (1) the familiar aggregation of erythrocyte sodium-lithium (Na,Li) countertransport; (2) the association of Na,Li countertransport with the presence of arterial hypertension and lipid abnormalities; (3) the correlation between Na,Li countertransport activity and renal functional reserve; and (4) the preliminary results of a longitudinal study. In 13 families of patients with IgA nephropathy, selected because both parents were available, we found a significant correlation between midparent and offspring Na,Li countertransport activity (Spearman's rank correlation = 0.65; P = 0.023), but no husband-wife relationship. In 49 patients, the activity of Na,Li countertransport was significantly higher in erythrocytes from 20 hypertensive patients than from either 29 normotensive patients or from 36 healthy age- and sex-matched normal subjects. Hyperlipidemic patients had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic patients and controls. In 17 patients a significant inverse correlation was found between the peak variation of creatinine clearance over baseline value after an oral protein load and the erythrocyte Na,Li countertransport activity (Spearman r = 0.54; P = 0.03). In a longitudinal study of 36 patients followed from 12 to 36 months, those showing a progression toward renal failure had an erythrocyte Na,Li countertransport activity higher than median value. The results of our studies show that in patients with IgA nephropathy a high erythrocyte Na,Li countertransport rate, genetically determined, is associated with the presence of arterial hypertension and lipid abnormalities, and perhaps with a less favorable disease outcome.

Aggregation of erythrocyte sodium/lithium countertransport activity in families of patients with immunoglobulin A nephropathy.

1. We evaluated the inheritance of erythrocyte Na+/Li+ countertransport activity in IgA nephropathy by assessing this parameter in 19 patients with biopsy-proven IgA nephropathy and in their 53 relatives (32 parents and 21 siblings). The possible use of erythrocyte Na+/Li+ countertransport activity as a marker of poor prognosis was also evaluated. 2. A significant correlation was found between 'familial' and proband Na+/Li+ countertransport activity, but not between that of spouses. 3. Mean blood pressure, although within the normal range, and Na+/Li+ countertransport activity were significantly higher in patients with proteinuria than in those without proteinuria. 4. Parents of proteinuric patients had a higher Na+/Li+ countertransport activity than parents of non-proteinuric patients. 5. In IgA nephropathy the inheritance of erythrocyte Na+/Li+ countertransport activity was preserved. Therefore genetic factors could play a role in the non-immunological progression of IgA nephropathy.

Increased sodium-lithium countertransport activity in red cells of IgA nephropathy patients.

The aim of this work was to analyze Na,Li countertransport activity in the erythrocytes from patients with IgA nephropathy, in relationship with their blood pressure status and lipid profile. Forty-nine patients (32 males, 17 females) with biopsy-proven IgA nephropathy and without significant impairment of renal function (serum creatinine less than or equal to 1.4 mg/dl) and 36 normal subjects (21 males, 15 females) were evaluated. Twenty-nine patients with IgA nephropathy were normotensive and 20 hypertensive (diastolic pressure greater than or equal to 95 mm Hg or treated by antihypertensive drugs). Na,Li countertransport was significantly higher in red cells from hypertensive than from normotensive patients (P = 0.002) and normal subjects (P = 0.0001), (values respectively 309 +/- 17; 241 +/- 12 and 211 +/- 11 mumol/liter RBC/hr); normotensive patients with IgA nephropathy did not differ from controls regarding the Na,Li countertransport rate. A multiple stepwise logistic regression analysis with blood pressure status as the dependent variable and Na,Li countertransport activity, age, serum creatinine, proteinuria, cholesterol, triglycerides, plasma potassium and time from onset as independent variables, indicated an independent significant association for Na,Li countertransport (P = 0.002) proteinuria (P = 0.006), plasma potassium (P = 0.006) and age (P = 0.029). Other tested variables were not independently related to blood pressure status. Hyperlipidemic patients (plasma total cholesterol concentration greater than 200 mg/dl and/or plasma triglycerides greater than 172 mg/dl) had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic (P = 0.005) and controls (P = 0.001) (values respectively 295 +/- 14; 226 +/- 12 and 211 +/- 11 mumol/liter RBC/hr).(ABSTRACT TRUNCATED AT 250 WORDS)