Pasquale Zamboli

Antiproteinuric response to dual blockade of the renin-angiotensin system in primary glomerulonephritis: meta-analysis and metaregression.

BACKGROUND In patients with primary glomerulonephritis (GN), antiproteinuric response to angiotensin-converting enzyme (ACE) inhibitors plus angiotensin receptor blockers (ARBs) versus either monotherapy is undefined because of the small size of studies and high heterogeneity of response. STUDY DESIGN Meta-analysis/metaregression. SETTING & POPULATION Randomized clinical trials (RCTs). SELECTION CRITERIA FOR STUDIES RCTs published from January 1996 to April 2007. Studies were excluded if information about levels of proteinuria was not available, patients had kidney disease other than primary GN, or if they had end-stage renal disease. INTERVENTION ACE inhibitor plus ARB versus monotherapy with 1 of these drug classes. OUTCOMES Absolute changes in proteinuria (primary), blood pressure, serum potassium level, and glomerular filtration rate (GFR; secondary). RESULTS We found 13 RCTs including 425 patients with primary GN with proteinuria ranging from 0.8 to 7.9 g/d of protein and age from 25 to 60 years. Combination treatment decreased proteinuria by 0.60 g/d (95% confidence interval, 0.40 to 0.80) versus ACE-inhibitor monotherapy and 0.54 g/d (95% confidence interval, 0.30 to 0.78) versus ARB monotherapy. Baseline levels of proteinuria explained most between-study variability of the antiproteinuric response to combination therapy versus monotherapies. Systolic and diastolic blood pressure, GFR, age, and diagnosis of immunoglobulin A nephropathy did not modify antiproteinuric response. ACE-inhibitor plus ARB therapy did not change GFR, whereas it increased serum potassium levels (by 0.10 mEq/L versus ACE-inhibitor and 0.19 mEq/L versus ARB therapy) and decreased blood pressure. LIMITATIONS Only published data are included. CONCLUSIONS The antiproteinuric response to ACE-inhibitor plus ARB therapy versus either monotherapy is consistently greater and strictly related to baseline proteinuria, associated with only moderate increase in serum potassium levels, and not peculiar to immunoglobulin A nephropathy.

Burden of Resistant Hypertension in Hypertensive Patients with Non-Dialysis Chronic Kidney Disease

Background/Aims: In chronic kidney disease (CKD), no data on resistant hypertension (RH) are so far available despite the high prevalence of uncontrolled hypertension. We evaluated frequency, correlates and prognosis of RH in 300 consecutive incident hypertensive CKD patients in an academic renal clinic. Methods: RH was defined as office blood pressure (BP) ≧130/80 mm Hg despite ≧3 drugs at full dose including a diuretic, or as BP at goal with ≧4 full-dose drugs. Patients were evaluated at referral and after 6 months of nephrology management; thereafter, they were included in a renal survival analysis lasting 37.6 months. Results: On referral, glomerular filtration rate was 41.3 ± 16.6 ml/min/1.73 m2 and BP 148 ± 23/81 ± 12 mm Hg. After 6 months, BP decreased by 8 ± 23/3 ± 12 mm Hg. From referral to month 6, RH detection increased from 26 to 38% due to the significant increment in full-dose antihypertensive medications (from 2.0, IQR 1.0–3.0 to 2.5, IQR 2.0–3.0). Diabetes and proteinuria predicted the incidence of RH at month 6. Presence of RH at month 6 was associated with greater risk of renal death (HR, 1.85, 95% CI, 1.13–3.03), independent of main clinical features and degree of BP control. Conclusion: In CKD, RH is prevalent and associated with decreased renal survival, independent of BP levels.

Conversion of Darbepoetin to Low Doses of CERA Maintains Hemoglobin Levels in Non-Dialysis Chronic Kidney Disease Patients

Background/Aims: Finding the lowest effective dose of erythropoietin-stimulating agents is critical in the management of renal anemia. We evaluated the efficacy of converting darbepoetin to CERA at doses lower than those usually recommended. Methods: We selected consecutive non-dialysis chronic kidney disease patients treated with darbepoetin doses ≤40 µg/week in absence of iron deficiency, recent blood transfusion, bleeding, neoplasia, myocardial infarction/stroke in the last 3 months. Darbepoetin ≤20 µg/week was shifted to CERA 75 µg/month, while darbepoetin 21–40 µg/week to CERA 100 µg/month. Primary endpoint was the change in hemoglobin (Hb goal, 11–13 g/dl) at month 3, 6, 9 and 12. Results: Studied patients (n = 37) were aged 70 ± 13 years and GFR was 30 ± 12 ml/min/1.73 m2; prevalence of males, diabetes and prior cardiovascular disease was 43, 45 and 40%, respectively. Before switching, efficacy population received darbepoetin 18 ± 10 µg/week with 28 patients receiving ≤20 µg/week. Prevalence of Hb goal at baseline was 75.7% and did not change at months 3 (70.3%), 6 (70.3%), 9 (72.2%), and 12 (80.0%). CERA dose remained unchanged during the study (81 ± 11, 82 ± 16, 91 ± 30, 90 ± 54 and 88 ± 61 µg/month). Out of the 438 visits performed, CERA dose was increased in 52 (11.9%) and reduced in 36 (8.2%) visits. Blood pressure, Hb, GFR, transferrin saturation and ferritin did not change. Conclusions: In chronic kidney disease patients treated with darbepoetin doses ≤40 µg/week, CERA can be efficaciously used at doses lower than those recommended.

Management of cardiovascular risk factors in advanced type 2 diabetic nephropathy: a comparative analysis in nephrology, diabetology and primary care settings.

Objectives Advanced diabetic nephropathy (DN) is characterized by a marked development of cardiovascular and renal disease. These patients are frequently managed by different health professionals with the consequence that the quality of care may differ substantially. To compare the management of cardiovascular risk factors in patients with type 2 DN and an estimated glomerular filtration rate (GFR) of 15–60 ml/min per 1.73 m2 followed in nephrology, diabetology and primary care. Methods This multicentre cross-sectional study verified the control of blood pressure (BP), total cholesterol, triglycerides, glycosylated haemoglobin A1c (HbA1c) and haemoglobin in patients exclusively followed in either nephrology (n = 266), diabetology (n = 246) or primary care (n = 195) of the same metropolitan area for at least 1 year. Results Primary care patients were older and had a greater prevalence of previous cardiovascular events. The GFR was lower in nephrology than in diabetology and primary care (33 ± 13 versus 47 ± 9 and 40 ± 12 ml/min per 1.73 m2, P < 0.0001). The prevalence of BP target (< 130/80 mmHg) was similarly low in nephrology, diabetology and primary care (14, 13 and 10%, P = 0.421) probably because of insufficient prescription of diuretics and low-salt diet. Whereas the prevalence of the triglycerides target was similar, that of total cholesterol (< 200 mg/dl) was larger in diabetology (63%) than in nephrology and primary care (59 and 46%, P = 0.003) because of greater statin prescription in hypercholesterolemic individuals (70, 50 and 41%, respectively, P = 0.002). The attainment of HbA1c less than 7% was less frequent in diabetology (32%) than in nephrology and primary care (61 and 46%, P = 0.0003) despite a more frequent prescription of insulin/oral agents in diabetology. The control of anaemia was better in diabetology. Multivariate analysis adjusted for the patient case-mix and physician-level clustering confirmed these differences except for anaemia. Conclusion Patients with advanced DN, despite the worst renal and cardiovascular prognosis, are at high risk of being under-treated independently of the type of clinical setting.

Prevalence and Prognosis of Mild Anemia in Non-Dialysis Chronic Kidney Disease: A Prospective Cohort Study in Outpatient Renal Clinics

Background/Aims: We evaluated prevalence and prognosis of mild anemia, defined as Hb (g/dl) 11–13.5 in males and 11–12 in females, in a prospective cohort of stage 3–5 chronic kidney disease (CKD) patients. Methods: We enrolled 668 consecutive patients in 25 renal clinics during 2003. Patients with frank anemia (Hb <11 or erythropoiesis-stimulating agents) at enrolment were excluded. Mild anemia was evaluated at two visits planned with an interval of 18 ± 6 months to identify four categories: no anemia at both visits, mild anemia at visit 1 resolving at visit 2 (RES), mild anemia persisting at both visits (PER), and progression from no anemia or mild anemia at visit 1 to mild or frank anemia at visit 2 (PRO). Results: Mild anemia was present in 41.3% at visit 1 and 34.1% at visit 2. We identified PER in 22% patients, RES in 10%, and PRO in 26%. In the subsequent 40 months, 125 patients developed end-stage renal disease (ESRD) and 94 died. At competing risk model, PER predicted ESRD (hazard ratio, HR, 1.82, 95% confidence interval, CI, 1.01–3.29) while PRO predicted both ESRD (HR 1.81, 95% CI 1.02–3.23) and death (HR 1.87, 95% CI 1.04–3.37). Conclusion: In non-dialysis chronic kidney disease, mild anemia is prevalent and it is a marker of risk excess when persistent or progressive over time.

Color Doppler ultrasound and arteriovenous fistulas for hemodialysis

Native arteriovenous fistula (AVF) is the vascular access of choice for hemodialysis patients. Compared with grafts and central venous catheters, AVFs last longer and are associated with fewer complications. The widespread use of the Doppler ultrasound (DUS) has increased the number of patients who are eligible for AVF by facilitating the identification of vessels that are suitable for fistula construction (preoperative vascular mapping). DUS can also extend native AVF survival by improving the early detection of complications (post-operative surveillance). It is the only imaging modality that furnishes both morphological and functional data on the native vascular access, and it is also the only imaging tool that can be used directly by the surgeon, an indisputable advantage. This review examines the numerous roles played by DUS in the construction and postoperative follow-up of AVFs, including preoperative vascular mapping, AVF maturation, and surveillance.RiassuntoLa FAV confezionata con vasi nativi rappresenta l’accesso vascolare di scelta per il paziente emodializzato in quanto, a parità di flusso, presenta minore incidenza di complicanze e più lunga sopravvivenza rispetto alle protesi ed ai cateteri venosi centrali. L’avvento del DUS nell’armamentario di chi si occupa di chirurgia degli accessi vascolari ha, da un lato, aumentato il numero di pazienti in cui si riesce a confezionare una FAV con vasi nativi (grazie all’individuazione di vasi idonei all’intervento mediante il mapping pre-chirurgico), e, dall’altro, ha migliorato la sopravvivenza delle FAV grazie alla diagnosi precoce (monitoraggio post-operatorio) delle complicanze dell’accesso vascolare. L’eco-color-Doppler è l’unica tecnica in grado di dare informazioni sia morfologiche che di funzionalità (flusso) dell’accesso vascolare; inoltre, è l’unica tecnica (tra quelle di diagnostica per immagini) direttamente gestibile dal chirurgo e ciò rappresenta sicuramente un valore aggiunto. Questa review fornisce una panoramica sulle possibili applicazioni del DUS nell’ambito del confezionamento e del follow-up delle FAV, con particolare riferimento al mapping pre-chirurgico, alla maturazione della FAV e al monitoraggio/sorveglianza della FAV.

Effects of age on hypertensive status in patients with chronic kidney disease.

Objective To evaluate effect of age on hypertensive status in chronic kidney disease (CKD). Methods We studied 459 prevalent CKD patients (stages 2–5, no dialysis), grouped by age (< 55, 55–64, 65–74, ≥ 75 years), undergoing clinical blood pressure (CBP) and ambulatory blood pressure (ABP) measurement. Results Prevalence of diabetes, left ventricular hypertrophy and previous cardiovascular disease progressively increased with aging; glomerular filtration rate (GFR) and hemoglobin decreased. Achievement of CBP target decreased from 16% in patients < 55 years to 6% in those ≥ 75 years (P = 0.023). ABP 24-h systolic rose while diastolic decreased, with a consequent pulse pressure increase from 45 ± 8 to 65 ± 14 mmHg (P < 0.0001). Age, proteinuria, diabetes, cardiovascular disease and anemia but not GFR predicted higher 24-h pulse pressure. CBP overestimated systolic/diastolic daytime ABP by 14 ± 18/7 ± 11 mmHg on average, a greater difference in older than younger groups (P < 0.005). Conversely, CBP night-time ABP difference did not vary among groups (24 ± 20/16 ± 11 mmHg). These age-dependent differences determined a rising prevalence of white-coat hypertension (from 19 to 40%, P = 0.001) and night/day ratio of at least 0.9 (from 43 to 66%, P = 0.0004). Age, diabetes, left ventricular hypertrophy and anemia but not GFR predicted nondipping status. Among the oldest patients, 13% had diastolic CBP below 70 mmHg, with 48% below the corresponding values of daytime (< 69 mmHg) or night-time ABP (< 60 mmHg). Conclusion In CKD, prevalence of white-coat hypertension, nondipping status and potentially dangerous low diastolic ABP increases with aging. This suggests wider use of ABP monitoring in older patients and need for trials addressing identification of an age-specific blood pressure target.

Effect of furosemide on left ventricular mass in non-dialysis chronic kidney disease patients: a randomized controlled trial

BACKGROUND In chronic kidney disease (CKD), loop diuretics correct volume-dependent hypertension, but their effect on left ventricular mass index (LVMI) is unknown. METHODS Forty hypertensive CKD patients (estimated creatinine clearance 60-15 mL/min/1.73 m²), treated with renin-angiotensin system (RAS) inhibitors, were randomized to receive furosemide or non-diuretic antihypertensive treatment (control group). Office blood pressure (BP) < 130/80 mmHg was pursued in both groups. Primary end point was the reduction of LVMI after 52 weeks. Secondary aims were to verify safety related to furosemide treatment and its effects on ambulatory and clinic BP and body fluid volumes. RESULTS Office BP similarly declined in the furosemide group (from 161 ± 14/80 ± 10 to 139 ± 14/74 ± 8 mmHg) and in controls (from 159 ± 16/81 ± 10 to 137 ± 16/75 ± 10 mmHg). We detected a greater reduction (P = 0.013) of LVMI in patients receiving furosemide (-7.9, IQR from -15.8 to -1.4 g/h(2.7)) than in controls (0.0, IQR from -6.2 to + 9.5 g/h(2.7), P = 0.013). Bio-impedance analysis-derived extracellular water (ECW) significantly decreased in furosemide-treated patients (from 18.7 ± 3.9 to 17.7 ± 3.3 L) while remained unchanged in the control group (from 19.5 ± 2.2 to 19.6 ± 1.9 L). Absolute change of LVMI correlated with changes of ECW in furosemide-treated patients (r = 0.458, P = 0.042) but not in controls. In the furosemide group, no patient experienced side effects requiring drug withdrawal. CONCLUSIONS In hypertensive CKD patients treated with RAS inhibitors, add-on furosemide efficaciously reduces LVMI independently from BP changes. The effect is possibly mediated by better control of volume expansion.

Intradialytic Changes of Plasma Amino Acid Levels: Effect of Hemodiafiltration with Endogenous Reinfusion versus Acetate-Free Biofiltration

During hemodialysis, amino acids (AA) are lost in the ultrafiltrate with consequent modification of their plasma profile. The aim of this cross-sectional study was to evaluate intradialytic changes of plasma AA levels during a single session of hemodiafiltration with endogenous reinfusion (HFR) versus acetate-free biofiltration (AFB). 48 patients chronically treated with HFR or AFB were matched 1:1 for age, gender, Kt/V and diabetes. Blood samples were collected at the beginning and the end of dialysis. Baseline plasma levels (µmol/l) of total AA (3,176 ± 722), essential AA (889 ± 221), and branched chain AA (459 ± 140) levels in HFR were similar to those in AFB (3,399 ± 621, 938 ± 277, and 463 ± 71, respectively). Plasma intradialytic AA levels did not change in HFR, while in AFB there was a reduction by about 25%. In conclusion, as compared with AFB, HFR has a sparing effect on AA loss due to the lack of adsorption by cartridge and to their complete reinfusion in blood.

Hypertension management in chronic kidney disease: translating guidelines into daily practice.

BACKGROUND Whether nephrology management improves over time achievement of blood pressure (BP) goal (<130/<80 mm Hg) in nondialysis CKD is still ill-defined. This historical cohort analysis evaluated the relationship between 1-year nephrology management and BP control in 275 incident CKD patients in an academic renal clinic. METHODS Comparative analysis between referral and month-12 visit. RESULTS Estimated glomerular filtration rate (GFR) was 42.1 ± 15.5 ml/min per 1.73 m2 and median proteinuria 0.20 g/24 hours. From baseline to month-12 visit, BP decreased from 148 ± 23 / 81 ± 12 mm Hg to 136 ± 18 / 76 ± 11 mm Hg, with BP goal prevalence increasing from 13.8% to 33.8%. We stratified patients into at-goal and not-at-goal on the basis of month-12 BP levels. Regression analysis identified diabetes (odds ratio [OR] = 1.96; 95% confidence interval [95% CI], 1.07-3.56) and basal systolic BP (OR=1.12; 95% CI, 1.03-1.21) as independent predictors of not-at-goal BP. The decrease in systolic/diastolic BP was smaller in not-at-goal versus at-goal patients (-7/3 mm Hg vs. -21/9 mm Hg); in not-at-goal reduction was, however, significant versus baseline (p<0.001) and coupled with a similar decline in proteinuria (p<0.001). CONCLUSIONS Sustained nephrology management improves hypertension control in CKD, but achievement of BP goals remains suboptimal, with high systolic BP and diabetes being the main problems. Further studies are needed to verify the clinical significance of BP and proteinuria changes in patients whose BP remains above target levels.