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Biomedical subjects

Annalisa Perna

Publications and source records attributed to Annalisa Perna.

At least 19 recordsLinked to original sources
PubMed2006

Impact of blood pressure control and angiotensin-converting enzyme inhibitor therapy on new-onset microalbuminuria in type 2 diabetes: a post hoc analysis of the BENEDICT trial.

For assessment of the independent renoprotective effect of BP control and angiotensin-converting enzyme inhibitor (ACEi) therapy, the relationships of baseline BP, BP reduction, and follow-up BP with the incidence of persistent microalbuminuria were evaluated in 1204 hypertensive patients who had type 2 diabetes and normoalbuminuria and were included in the BErgamo Nephrologic Diabetic Complications Trial (BENEDICT) study and were randomly assigned to 3.6 yr of treatment with the ACEi trandolapril (2 mg/d), the nondihydropyridine calcium channel blocker (ndCCB) verapamil SR (240 mg/d), their fixed combination Veratran (trandolapril 2 mg/d plus verapamil SR 180 mg/d), or placebo, plus other antihypertensive medications targeted at systolic/diastolic BP <130/80 mmHg. Follow-up (from month 3 to study end) systolic, diastolic, mean, and pulse BP and their reductions versus baseline--but not baseline BP--independently predicted (P < 0.001) the risk for microalbuminuria. In patients with follow-up BP above medians, ACEi significantly reduced the risk for microalbuminuria to levels that were observed among patients with BP below medians, regardless of ACEi treatment. The same trend was observed among patients with BP reductions below medians. ndCCB therapy did not independently affect microalbuminuria. Patients who were on Veratran had lower BP and less frequently received diuretics, beta blockers, or dihydropyridine dCCB. In hypertensive, normoalbuminuric patients with type 2 diabetes, BP reduction and ACEi therapy both independently may prevent microalbuminuria. ACEi therapy is particularly effective when BP is poorly controlled, whereas ndCCB therapy is ineffective at any level of achieved BP. As compared with trandolapril, Veratran may help with achievement of target BP with less need for concomitant antihypertensive medications.

Albuminuria↗
PubMed2006

Long-term outcome of renal transplantation from older donors.

BACKGROUND: Long-term survival of kidney grafts from older donors is inferior to that of grafts from younger donors. We sought to determine whether selecting older kidneys according to their histologic characteristics before implantation would positively influence long-term outcome. METHODS: In a prospective cohort study, we assessed outcomes among 62 patients who received one or two histologically evaluated kidneys from donors older than 60 years of age. These outcomes were compared with outcomes among 248 matched recipients of single kidney grafts that had not been histologically evaluated and were either from donors 60 years of age or younger (124 positive-reference recipients who, according to available data, were expected to have an optimal outcome) or from those older than 60 years (124 negative-reference recipients, expected to have a worse outcome). The primary end point was graft survival. RESULTS: During a median period of 23 months, 4 recipients (6 percent) of histologically evaluated kidneys progressed to dialysis, as compared with 7 positive-reference recipients (6 percent) and 29 negative-reference recipients (23 percent). Graft survival in recipients of histologically evaluated kidneys did not differ significantly from that of grafts in positive-reference recipients but was superior to that of grafts in negative-reference recipients (hazard ratio for graft failure in the negative-reference recipients relative to the recipients of histologically evaluated kidneys, 3.68; 95 percent confidence interval, 1.29 to 10.52; P=0.02). The performance of preimplantation histologic evaluation predicted better survival both in the whole study group (P=0.02) and among recipients of kidneys from older donors (P=0.01). CONCLUSIONS: The long-term survival of single or dual kidney grafts from donors older than 60 years of age is excellent, provided that the grafts are evaluated histologically before implantation. This approach may help to expand the donor-organ pool for kidney transplantation.

Age Factors↗
PubMed2006

Liver involvement in hereditary hemorrhagic telangiectasia: consensus recommendations.

STUDY PURPOSE: To formulate recommendations about clinical management of liver involvement in hereditary hemorrhagic telangiectasia (HHT), using a formal consensus development process. CONSENSUS PROCESS: A nominal group technique was used. A list of main clinical, diagnostic and therapeutic issues about liver involvement in HHT was generated by the organizing committee. Panel members then scored their agreement with each statement; the median score, and standard deviation for each statement were determined for each of the three successive panel rounds. These consensus statements formed the basis for recommendations graded with the strength and quality of supporting evidence. RECOMMENDATION STATEMENTS: Doppler US is sufficiently accurate and suitable for first-line imaging of the liver in the general HHT population. Liver biopsy in any patient with proven or suspected HHT should be avoided. Liver involvement in HHT is generally asymptomatic; in the minority of patients where it is symptomatic, morbidity and mortality can be substantial. The prevalence of focal nodular hyperplasia is much higher in patients with liver involvement by HHT than in the general population. Invasive therapies for liver involvement by HHT (namely liver transplantation) should be considered only in patients who have failed to respond to intensive medical therapy.

Cholestasis↗
PubMed2005

Does the Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism modify the response to ACE inhibitor therapy?--A systematic review.

BACKGROUND: Pharmacogenetic testing to individualize ACE inhibitor therapy remains controversial. We conducted a systematic review to assess the effect modification of the insertion/deletion (I/D) polymorphism of the ACE gene on any outcome in patients treated with ACE inhibitors for cardiovascular and/or renal disease. METHODS: Our systematic review involved searching six electronic databases, then contacting the investigators (and pharmaceutical industry representatives) responsible for the creation of these databases. Two reviewers independently selected relevant randomized, placebo-controlled trials and abstracted from each study details on characteristics and quality. RESULTS: Eleven studies met our inclusion criteria. Despite repeated efforts to contact authors, only four of the eleven studies provided sufficient data to quantify the effect modification by genotypes. We observed a trend towards better response to ACE inhibitors in Caucasian DD carriers compared to II carriers, in terms of blood pressure, proteinuria, glomerular filtration rate, ACE activity and progression to end-stage renal failure. Pooling of the results was inappropriate, due to heterogeneity in ethnicity, clinical domains and outcomes. CONCLUSION: Lack of sufficient genetic data from the reviewed studies precluded drawing any convincing conclusions. Better reporting of genetic data are needed to confirm our preliminary observations concerning better response to ACE inhibitors among Caucasian DD carriers as compared to II carriers.

Journal Article↗
PubMed2004

Preventing microalbuminuria in type 2 diabetes.

BACKGROUND: The multicenter double-blind, randomized Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) was designed to assess whether angiotensin-converting-enzyme inhibitors and non-dihydropyridine calcium-channel blockers, alone or in combination, prevent microalbuminuria in subjects with hypertension, type 2 diabetes mellitus, and normal urinary albumin excretion. METHODS: We studied 1204 subjects, who were randomly assigned to receive at least three years of treatment with trandolapril (at a dose of 2 mg per day) plus verapamil (sustained-release formulation, 180 mg per day), trandolapril alone (2 mg per day), verapamil alone (sustained-release formulation, 240 mg per day), or placebo. The target blood pressure was 120/80 mm Hg. The primary end point was the development of persistent microalbuminuria (overnight albumin excretion, > or =20 microg per minute at two consecutive visits). RESULTS: The primary outcome was reached in 5.7 percent of the subjects receiving trandolapril plus verapamil, 6.0 percent of the subjects receiving trandolapril, 11.9 percent of the subjects receiving verapamil, and 10.0 percent of control subjects receiving placebo. The estimated acceleration factor (which quantifies the effect of one treatment relative to another in accelerating or slowing disease progression) adjusted for predefined baseline characteristics was 0.39 for the comparison between verapamil plus trandolapril and placebo (P=0.01), 0.47 for the comparison between trandolapril and placebo (P=0.01), and 0.83 for the comparison between verapamil and placebo (P=0.54). Trandolapril plus verapamil and trandolapril alone delayed the onset of microalbuminuria by factors of 2.6 and 2.1, respectively. Serious adverse events were similar in all treatment groups. CONCLUSIONS: In subjects with type 2 diabetes and hypertension but with normoalbuminuria, the use of trandolapril plus verapamil and trandolapril alone decreased the incidence of microalbuminuria to a similar extent. The effect of verapamil alone was similar to that of placebo.

Adult↗
PubMed2004

Continuum of renoprotection with losartan at all stages of type 2 diabetic nephropathy: a post hoc analysis of the RENAAL trial results.

Renin angiotensin system inhibitor therapy is seldom offered to individuals who have diabetes and advanced chronic kidney disease because of safety concerns. In this post hoc, secondary analysis of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial, angiotensin antagonism risk/benefit profile was assessed in 1513 individuals with type 2 diabetes and overt nephropathy. Incidence of ESRD, hospitalizations for heart failure, withdrawals for adverse events, and proteinuria during losartan or conventional treatment were compared within three tertiles of baseline serum creatinine concentration (highest, 2.1 to 3.6 mg/dl; middle, 1.6 to 2.0 mg/dl; lowest, 0.9 to 1.6 mg/dl). Losartan decreased the risk of ESRD by 24.6, 26.3, and 35.3% in highest, middle, and lowest tertiles, respectively. For every 100 patients with serum creatinine >2.0, 1.6 to 2.0, or <1.6 mg/dl, respectively, 4 yr of losartan therapy was estimated to save 18.9, 8.4, and 2.9 ESRD events and US$1,502,855, US$1,021,770, and US$528,591 costs for renal replacement therapy. Losartan also decreased the hospitalizations for heart failure by 50.2 and 45.1, in the highest and middle tertile, respectively. Withdrawals for adverse events other than heart failure were comparable between tertiles and treatment groups. Proteinuria decreased more on losartan than on placebo in all tertiles (highest, 24 versus -8%; middle, 16 versus -8%; lowest, 15 versus -10%). In proteinuric individuals with type 2 diabetes, losartan therapy reduced ESRD and hospitalizations for heart failure and was well tolerated at all levels of renal function. Angiotensin II antagonism is a suitable and well-tolerated treatment for individuals with type 2 diabetes even with GFR levels approaching renal replacement therapy.

Aged↗
PubMed2004

Immunosuppressive treatment for idiopathic membranous nephropathy: a systematic review.

BACKGROUND: This study aims to assess whether immunosuppression is beneficial in the treatment of idiopathic membranous nephropathy (IMN). METHODS: We reviewed randomized controlled trials (RCTs) addressing the effect of immunosuppression on histologically proven IMN in adults with nephrotic syndrome followed up for at least 6 months. The literature was searched according to Cochrane Collaboration guidelines. Four therapeutic classes were considered: (1) steroids (alone), (2) alkylating agents (alone or in combination with steroids), (3) calcineurin inhibitors (alone or in combination with steroids), and (4) antiproliferative agents (alone). RESULTS: Eighteen RCTs were selected (1,025 patients). Overall, no differences were found between immunosuppressive treatment and placebo or no treatment. For oral glucocorticoid therapy, no beneficial effect was observed. For alkylating agents, a beneficial effect was observed on complete remission (relative risk [RR], 2.37; 95% confidence interval [CI], 1.32 to 4.25; P = 0.004). Excluding patients with particularly well-preserved renal function, there was no significant difference in complete remission. Cyclophosphamide therapy resulted in a lower rate of adverse-event discontinuations compared with chlorambucil (8 versus 21 discontinuations, respectively; RR, 2.34; 95% CI, 1.25 to 4.39; P = 0.008). For calcineurin inhibitors, no difference was observed. For antiproliferative agents, a paucity of data did not allow a conclusion. CONCLUSION: The meta-analysis failed to show a long-term effect of treatment on patient and/or renal survival. There is weak evidence that the immunosuppressive regimen increased the remission rate. The review of safety showed a higher number of discontinuations for adverse events in immunosuppressive-treatment groups and that cyclophosphamide had fewer side effects than chlorambucil.

Alkylating Agents↗
PubMed2003

Diverse effects of increasing lisinopril doses on lipid abnormalities in chronic nephropathies.

BACKGROUND: Dyslipidemia frequently complicates chronic nephropathies and increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as angiotensin-converting enzyme inhibitors, which effectively reduce proteinuria. METHODS AND RESULTS: In this longitudinal study, we evaluated the extent to which uptitration of the ACE inhibitor lisinopril to maximum tolerated doses (median [range]: 30 [10 to 40] mg/d) ameliorated proteinuria and dyslipidemia in 28 patients with nondiabetic chronic nephropathies. Maximum lisinopril doses significantly and safely reduced proteinuria, serum total, LDL cholesterol, and triglycerides without substantially affecting serum HDL and renal hemodynamics. Proteinuria already decreased at 10 mg/d. Serum lipids progressively and dose-dependently decreased during uptitration to maximum doses. Reduction in total and LDL cholesterol correlated with increases in serum albumin/total protein concentration and oncotic pressure, peaked at lisinopril maximum doses, and persisted after treatment withdrawal. Despite less proteinuria reduction, hypercholesterolemia decreased more (and reflected the increase in serum albumin) in hypoalbuminemic than in normoalbuminemic patients who, despite more proteinuria reduction, had less decrease in cholesterol and no changes in serum albumin. Changes in serum triglycerides were independent of changes in serum proteins, were strongly correlated with lisinopril doses (r=-0.89, P=0.003) and recovered promptly after treatment withdrawal. Lisinopril was well tolerated, did not affect renal hemodynamics, and caused symptomatic, reversible hypotension in only two patients. CONCLUSIONS: In chronic nephropathies, angiotensin converting enzyme inhibitor uptitration to maximum tolerated doses safely ameliorated hypertriglyceridemia by a direct, dose-dependent effect, and hypercholesterolemia through amelioration of the nephrotic syndrome, particularly in patients with more severe hypoalbuminemia.

Adolescent↗
PubMed2003

Nonimmunosuppressive therapy of membranous nephropathy.

Idiopathic membranous nephropathy (MN) has a variable rate of progression to end-stage renal failure, with a significant number of patients going into spontaneous remission without therapy. For those who have persistent nephrotic proteinuria or manifest deterioration of renal function, steroids and immunosuppressive drugs are used. However, their long-term efficacy is challenged by a meta-analysis presented here. A different approach to reduction of proteinuria, a recognized progression promoter, is based on the notion that angiotensin II inhibition controls proteinuria and slows progression. Further, a more complex approach is required than simple administration of an angiotensin-converting enzyme (ACE) inhibitor: a multidrug approach to remission of nephrotic syndrome therefore is described here.

Adult↗
PubMed2003

Retarding progression of chronic renal disease: the neglected issue of residual proteinuria.

BACKGROUND: Findings that early changes in proteinuria independently predict long-term glomular filtration rate (GFR) decline (Delta GFR) would highlight proteinuria as a major determinant of progression in chronic renal disease. METHODS: We investigated whether percent changes (3 months vs. baseline) in proteinuria (adjusted for concomitant changes in GFR) and residual proteinuria at 3 months, predicted Delta GFR [over a median (IQ range) follow up of 31.3 (24.5 to 50.3) months] in 273 patients with proteinuric chronic nephropathies enrolled in the Ramipril Efficacy In Nephropathy (REIN) study. RESULTS: Short-term changes and residual proteinuria (r = -0.23, P = 0.0001 for both) significantly correlated with Delta GFR and, at multivariate analyses, independently predicted Delta GFR (beta = -0.23, P = 0.0002; beta = -0.21, P = 0.0004, respectively). For comparable levels of residual proteinuria, patients with greater short-term reduction had slower Delta GFR (-0.28 +/- 0.04 mL/min/1.73 m2/ vs. -0.53 +/- 0.07 mL/min/1.73 m2/month, P = 0.04). On ramipril and conventional treatment, specular short-term changes in proteinuria (-18.2 +/- 3.5% vs. 24.2 +/- 6.7%, P < 0.0001, respectively) were associated with significantly different Delta GFRs. However, similar changes in proteinuria resulted in a difference in Delta GFR (ramipril, 0.39 +/- 0.07 mL/min/1.73 m2/month; conventional therapy, 0.74 +/- 0.11 mL/min/1.73 m2/month; P < 0.01) that was sevenfold higher (0.35 vs. 0.05 mL/min/1.73 m2/month) in patients with basal proteinuria > or =3 g/24 hours as compared to those with basal proteinuria 1 to 3 g/24 hours (ramipril, 0.25 +/- 0.06 mL/min/1.73 m2/month; conventional therapy, 0.30 +/- 0.07 mL/min/1.73 m2/month; P = NS). CONCLUSION: Regardless of blood pressure control and treatment randomization, short-term changes in proteinuria and residual proteinuria reliably predict long-term disease progression. Reducing proteinuria is renoprotective, particularly in nephrotic patients. As for arterial hypertension, proteinuria should be a specific target for renoprotective treatment.

Adolescent↗
PubMed2003

Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies.

BACKGROUND: Proteinuria predicts renal disease progression, and its reduction by angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARA) is renoprotective. METHODS: In this prospective, randomized, cross-over study of 24 patients with nondiabetic, chronic nephropathies, we compared the effects on proteinuria, renal hemodynamics, and glomerular permselectivity of 8 weeks with comparable blood pressure control achieved by benazepril (10 mg/day) and valsartan (80 mg/day) combined therapy with those achieved by benazepril (20 mg/day) or valsartan (160 mg/day) alone. RESULTS: Despite comparable changes in blood pressure and glomerular filtration rate (GFR), combined therapy decreased proteinuria more than benazepril (-56% vs. -45.9%, P=0.02) and valsartan (-41.5%, P=0.002). Changes in urinary protein to creatinine ratio followed the same trend. Filtration fraction and renal vascular resistances (RVR) decreased more with combined (-14.7%,-23.7%) or benazepril (-12.4%, -20.5%) than with valsartan (-2.7%, -12.5%, P < 0.05 vs. both). RVR changes, adjusted for GFR changes, were associated with those in proteinuria (P < 0.05). Changes in glomerular permeability were comparable and did not predict different changes in proteinuria in the three groups. CONCLUSION: At comparable blood pressure, combined ACEi and ARA decreased proteinuria better than ACEi and ARA. The greater antiproteinuric effect most likely depended on an ACEi-related hemodynamic effect, in addition to glomerular size selectivity amelioration. Long-term combined ACEi and ARA therapy may be more renoprotective than treatment with each agent alone.

Adult↗
PubMed2003

Predicting end-stage renal disease: Bayesian perspective of information transfer in the clinical decision-making process at the individual level.

BACKGROUND: Predicting outcomes such as end-stage renal disease (ESRD) by integration and better utilization at individual level of epidemiologic data may facilitate clinical decision-making processes. METHODS: To predict individual ESRD risk in an average patient in the United States, ESRD prevalence and levels of uncertainty and conditional risk factors independence were considered by population data (1998) and pooled analysis of 11 randomized trials. Data integration and input were by decision-tree simulation approach (simple, parallel, and sequential scenarios) and Bayes' theorem. Sensitivity analysis and risk profiles were employed to address uncertainty and assess different risk factor combinations. A health state values, associated with ESRD outcome levels, were taken from the literature. RESULTS: In this theoretical study, we provided a scholarly example about the use of two known risk factors (urinary protein >/=3 g/day and systolic blood pressure >/=140 mm Hg) to predict individual ESRD risk in an average patient in the United States. The highest posterior (decisional) probability of ESRD occurrence (risk of 3.61% to 5.07%) in the individual patient was associated with the worst health state, as assessed by multidimensional scenarios when both risk factors were present. CONCLUSION: Decision tree models through an empirical Bayesian approach may serve to predict the individual ESRD risk on the basis of simple epidemiologic, demographic, and clinical information that is easily available already at the first patient evaluation.

Algorithms↗
PubMed2003

Renal transplantation: can we reduce calcineurin inhibitor/stop steroids? Evidence based on protocol biopsy findings.

How to combine antirejection drugs and which is the optimal dose of steroids and calcineurin inhibitors beyond the first year after kidney transplantation to maintain adequate immunosuppression without major side effects are far from clear. Kidney transplant patients on steroid, cyclosporine (CsA), and azathioprine were randomized to per-protocol biopsy (n = 30) or no-biopsy (n = 29) 1 to 2 yr posttransplant. Steroid or CsA were discontinued or reduced on the basis of biopsy to establish effects on drug-related complications, acute rejection, and graft function over 3 yr of follow-up. Serum creatinine, GFR (plasma clearance of iohexol), RPF (renal clearance of p-aminohippurate), CsA pharmacokinetics, and adverse events were monitored yearly. At the end, patients underwent a second biopsy. Per-protocol biopsy histology revealed no lesions (n = 5, steroid withdrawal), CsA nephropathy (n = 13, CsA discontinuation/reduction), or chronic rejection (n = 12, standard therapy). Reducing the drug regimen led to overall fewer side effects related to immunosuppression as compared with standard therapy or no-biopsy. Steroids were safely stopped with no acute rejection or graft loss. Complete CsA discontinuation was associated with acute rejection in the first four patients. Lowering CsA to low target CsA trough (30 to 70 ng/ml) never led to acute rejection or major renal function deterioration. Biopsy patients on conventional regimen had no acute rejection, one graft loss, no significant change in GFR, and significant RPF decline. No-biopsy controls: no acute rejection, one graft loss, significant decline of GFR and RPF. By serial biopsy analysis, severe lesions did not develop in patients with steroid discontinuation in contrast to patients on standard therapy over follow-up. CsA reduction did not adversely affect histology. Per-protocol biopsy more than 1 yr after kidney transplantation is a safe procedure to guide change of drug regimen and to lower the risk of major side effects.

Adult↗
PubMed2003

Rituximab in idiopathic membranous nephropathy: a one-year prospective study.

Currently available monoclonal antibodies against the B cell surface antigen CD20 have been employed to explore whether specific inhibition of B cells may help improve the outcome of idiopathic membranous nephropathy (IMN) and may avoid the side effects of steroids and immunosuppressants. This prospective, observational study evaluated the 1-yr outcome of eight IMN patients with persistent (>6 mo) urinary protein excretion > 3.5 g/24 h given four weekly infusions of the anti-CD20 antibody rituximab (375 mg/m(2)). At 3 and 12 mo, proteinuria significantly decreased from mean (+/- SD) 8.6 +/- 4.2 to 4.3 +/- 3.3 (-51%, P < 0.005) and 3.0 +/- 2.5 (-66%, P < 0.005) g/24 h, albumin fractional clearance from 2.3 +/- 2.1 to 1.2 +/- 1.7 (-47%, P < 0.05) and 0.5 +/- 0.6 (-76%, P < 0.003), and serum albumin concentration increased from 2.7 +/- 0.5 to 3.1 +/- 0.3 (+21%, P < 0.05) and 3.5 +/- 0.4 (+41%, P < 0.05) mg/dl. At 12 mo, proteinuria decreased to < or =0.5 g/24 h or < or =3.5 g/24 h in two and three patients, respectively. Proteinuria decreased in the remaining patients by 74%, 44%, and 41%, respectively. Body weight, diastolic BP, and serum cholesterol progressively decreased in parallel with an improvement of edema in all patients. Renal function stabilized (Delta1/creatinine: +0.002 +/- 0.007). CD20 B lymphocytes fell below normal ranges up to study-end. No patient had major drug-related events or major changes in other laboratory parameters. Rituximab thus promotes sustained disease remission in patients otherwise predicted to progress to ESRD, and it is safe. The long-term risk/benefit profile of this novel, disease-specific approach seems much more favorable to that of commonly employed immunosuppressive drugs.

Adult↗
PubMed2003

Chronic nephropathies: individual risk for progression to end-stage renal failure as predicted by an integrated probabilistic model.

BACKGROUND/AIMS: To predict risk of end-stage renal disease (ESRD) in individual patients with chronic nephropathy. METHODS: Sequential use of univariate analyses and Cox regression to identify risk factors, artificial neural network to quantify their relative importance and Bayesian analysis to address uncertainty of relationships and incorporate ESRD prevalence information in 344 patients with chronic nephropathy enrolled in the Ramipril Efficacy In Nephropathy study. RESULTS: Serum creatinine (SC), 24-hour urinary protein excretion (UPE) and calcium-phosphorus (Ca*P) product were, in this order, the strongest time-adjusted ESRD predictors. Individual risk of ESRD ranged from near zero when SC and UPE were <1.66 mg/dl and <3 g/24 h, to 69% when SC, UPE and Ca*P were > or =2.41 mg/dl, > or =3 g/24 h and > or =32.64 mg2/dl2, respectively. Receiver operating characteristic curves showed that within lowest, middle and highest tertiles of basal SC (0.90-1.65, 1.66-2.40 and 2.41-6.30 mg/dl, respectively) the model accurately predicted ESRD (AUC = 0.80, 0.72 and 0.65; p = 0.0003, 0.0001 and 0.0022, respectively), quality of life or treatment costs. CONCLUSION: Integrated use of regression analysis and probabilistic models allows computation of individual risk of progression to ESRD and related utilities. This may help in optimizing care and costs in nephrology and other medical areas and designing trials in high-risk patients.

Analysis of Variance↗
PubMed2002

Angiotensin-converting-enzyme inhibition therapy in altitude polycythaemia: a prospective randomised trial.

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors reduce packed cell volume and haemoglobin concentration in polycythaemia that follows renal transplantation, which, like altitude polycythaemia, is an erythropoietin-dependent form of polycythaemia. We aimed to establish the effect of ACE-inhibitor treatment in people with altitude polycythaemia. METHODS: We did a prospective randomised study in 26 people with altitude polycythaemia (packed cell volume > or = 55%) and 24-h rate of urinary protein excretion greater than 150 mg, who had been referred to the Renal Disease Project in La Paz, Bolivia. 13 participants were assigned 5 mg/day enalapril for 2 years (study group), and 13 no treatment (controls). Blood pressure, packed cell volume and haemoglobin concentration, proteinuria, and renal function were compared by intention-to-treat analyses. FINDINGS: Baseline packed cell volume and haemoglobin concentration were positively correlated with bodyweight (p=0.02), systolic (p=0.01) and diastolic (p=0.04) blood pressure, serum creatinine (p=0.009), blood urea (p=0.008), and proteinuria (p=0.003). Systolic and diastolic blood pressure remained stable in the study group, but increased in controls. In study patients, mean (SD) packed cell volume, haemoglobin concentration, and proteinuria fell from 63.5% (4.9) to 56.8% (4.1), p<0.0001; 207 (18) to 164 g/L (13), p<0,0001; and from 358.6 (260.3) to 247.7 mg/24-h (208.2), p<0.002, respectively, but did not change significantly in controls. At 12 and 24 months of follow-up, packed cell volume, haemoglobin concentration, and proteinuria differed significantly between the groups (p<0.0001 for each comparison). In study patients, follow-up changes in packed cell volume (r=0.88, p<0.0001) or haemoglobin concentration (r=0.83, p<0.0001) and proteinuria were strongly correlated. Enalapril was well tolerated by all patients. INTERPRETATION: ACE-inhibition therapy effectively and safely ameliorates altitude polycythaemia and reduces proteinuria.

Adult↗