pCO2 Reveals Arteriovenous Fistula Recirculation in Bicarbonate Hemodialysis (RecirCO2lation Test).

We propose arterial pCO2 as test to discover vascular access recirculation (VAR) in bicarbonate hemodialysis (HD). We selected 30 HD patients with a ascertained well-functioning arteriovenous fistula (Control). In these patients, we artificially created VAR through the reversion of HD lines (Reversed). Results of the arterial gas analysis were collected at the start of HD (baseline) and after 5 min. At baseline, no differences of pH, pCO2 and HCO3 were found between the 2 groups. At 5 min, pCO2 increased from 38.1 ± 3.3 to 47.2 ± 6.3 mm Hg (p < 0.0001) in Reversed, whereas no increase was found in Control (p = 0.052). Areas under curve of pCO2-increase was 0.96 (0.91-1.00) and pCO2 at 5 min 0.92 (0.85-0.98). pCO2-increase >4.5 mm Hg showed sensitivity 86.7% and specificity 100% with positive predictive value (PPV) 100% and negative predictive value (NPV) 89%. A pCO2 value above 43 mm Hg at 5 min showed sensitivity 80%, specificity 90%, PPV 89%, NPV 82%. pCO2 increase >4.5 mm Hg and/or pCO2 at 5 min >43 mm Hg may accurately detect VAR.

Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis.

IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5×10⁻³²-3×10⁻¹°), with heterogeneity detected only at the PSMB9/TAP1 locus (I²â€Š= 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5×10⁻4). A seven-SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3×10⁻¹²8). This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.

Color Doppler ultrasound evaluation of arteriovenous grafts for hemodialysis.

Although arteriovenous fistula (AVF) continues to be the vascular access of choice for the hemodialysis, arteriovenous graft (AVG) can be the best choice in certain categories of patients and could have several advantages over AVF in a "patient centered approach" to vascular access. In the clinical management of prosthetic fistulas, color Doppler ultrasound (CDU) is the imaging method of choice for identifying stenosis and other AVG complications. In this review, besides highlighting the pivotal role of CDU in the diagnosis of AVG complications, we will underline the key role that ultrasound can play in identifying those stenosis most likely to cause AVG thrombosis. Furthermore, we will emphasize the support that CDU can play in distinguishing the different types of grafts and prosthetic devices such as stent-grafts, in identifying AVG with lower survival, CDU utilities and limitations in the evaluation of freshly-implanted grafts, the different sites available for AVG volume flow measurement and their use based on the configuration of the prosthesis, the time interval elapsed from the surgical intervention and the integrity of the prosthetic walls.

Indication to renal biopsy in DM2 patients: potential role of intrarenal resistive index.

Diagnosis of diabetic nephropathy is generally based, rather than on histological confirmation, on clinical criteria (long history of diabetes, presence of proteinuria, diabetic retinopathy or peripheral neuropathy). This clinical approach has perhaps limited utility in DM2 patients, because only 50% of them show microvascular complications in presence of nephropathy. Eco-colour-Doppler sampling of interlobular renal arteries and determination of their resistance indices (RI), was proposed in the differential diagnosis of numerous nephropathies. Aim of this study was to evaluate whether RI can be useful in discerning non-diabetic renal disease (NDRD), in order to better define indications to perform renal biopsy among proteinuric DM2 patients. All patients were submitted to: echo-colour-Doppler study of renal vessels; systematic screening for diabetic retinopathy; needle renal biopsy. RI resulted to be significantly higher in diabetic glomerulosclerosis (GSD) group as compared with NDRD group, while no significant difference was found with respect to NDRDs overlapping GSD (overlapping group). The last one showed however median RI significantly higher than isolated NDRD group. Normalized chi square Pearson for the hypothesis that RI can predict GSD resulted 0.73, while it resulted 0.43 for the hypothesis that diabetic retinopathy can predict GSD. Echo-colour-Doppler can significantly contribute, more than the other parameters proposed (nephritic or nephrotic syndrome, hematuria, diabetic retinopathy), to the identification of underlying nephropathy in DM2 subjects. In the light of our experience, it seems that the detection of RI values > 0.72 suggests the diagnosis of GSD or mixed forms, reducing the indications to renal biopsy only in presence of values < 0.72.

[Color-Doppler imaging and arteriovenous fistula: preoperative evaluation and surveillance]. / Eco-color-Doppler e fistola artero-venosa: utilizzo pre e post-chirurgico.

The native arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis because of the lower incidence of complications and longer survival in comparison to grafts and central venous catheters. The use of color-Doppler sonography in the surgery of vascular accesses has increased the number of patients that are eligible for AVF as it allows to optimize the search for vessels suitable for surgical intervention (preoperative vascular mapping). Furthermore, color-Doppler imaging (CDI) has improved the survival of native AVF by increasing the early diagnosis of complications (postoperative surveillance). CDI is the only imaging technique able to provide both morphological and functional information about native vascular access and it is the only tool directly available to the nephrologist. This aspect is undoubtedly an additional value. Here we present a survey of the applications of CDI in the surgery and followup of AVF, with particular reference to preoperative mapping, AVF maturation and surveillance.

[Management of color-Doppler imaging in dialysis patients]. / Il nefrologo e la gestione ecocolorDoppler del paziente in dialisi.

In recent decades, the survival of dialysis patients has gradually increased thanks to the evolution of dialysis techniques and the availability of new drug therapies. These elements have led to an increased incidence of a series of dialysis-related diseases that might compromise the role of dialysis rehabilitation: vascular disease, skeletal muscle disease, infectious disease, cystic kidney disease and cancer. The nephrologist is therefore in charge of a patient group with complex characteristics including the presence of indwelling vascular and/or peritoneal catheters, conditions secondary to chronic renal failure (hyperparathyroidism, anemia, amyloid disease, etc.) and superimposed disorders due to old age (cardiac and respiratory failure, cancer, type 2 diabetes mellitus, etc.). Early clinical and organizational management of such patients is essential in a modern and ''economic'' vision of nephrology. The direct provision of ultrasound services by the nephrologist responds to these requirements. A minimum level of expertise in diagnostic ultrasonography of the urinary tract and dialysis access should be part of the nephrologist's cultural heritage, acquired through theoretical and practical training programs validated by scientific societies, especially for those who choose to specialize in these procedures and become experts in imaging or interventional ultrasonography.

[Use of ECG-EC in the positioning of central venous catheters]. / Elettrocardiografia endocavitaria nel posizionamento dei cateteri venosi centrali.

Central venous catheters (CVC) are widely used in clinical practice for the administration of chemotherapy, parental nutrition, hemodynamic monitoring, and hemodialysis. International guidelines have defined the right internal jugular vein as the preferred site of CVC insertion and underline that accurate positioning of the catheter tip is essential to maximize the blood flow and reduce long-term complications. Endocavitary electrocardiography (EC-ECG) improves the accuracy of catheter tip positioning without increasing the placement time by the recognition of typical P wave patterns during catheter insertion:the normally shaped P wave identifies the mid to upper superior vena cava, the widest P wave may be used to place the CVC tip at the superior vena cava-right atrium junction, and biphasic P waves identify the location of the right atrium. Because of its simplicity and safety, EC-ECG should always be considered during CVC placement, especially if other means of verifying correct CVC insertion are not available.

[Contrast enhanced ultrasound in renal diseases]. / L'imaging ecocontrastografico nella patologia renale.

Contrast-enhanced ultrasound (CEUS) is one of the most interesting and promising clinical applications of imaging and ultrasound. Thanks to the absence of ionizing radiation, the lack of nephrotoxicity and low cost it has the potential to become a reference in imaging of the kidney. This review, besides providing a brief description of the proper methodology, presents possible applications of CEUS in nephrology and urology, including renal ischemia, the differential diagnosis of cystic and solid lesions, follow-up of ablative therapies, kidney trauma, kidney transplant, inflammatory diseases, ischemic nephropathy and vesicoureteral reflux.

[Ultrasound assessment in renal infections]. / L'ecografia nelle infezioni del rene.

Urinary tract infections (UTIs) are a common clinical problem, especially among women. Ultrasound assessment is indicated in case of complicated UTIs, in particular in children, pregnant women and patients with chronic kidney disease. Even though B-mode imaging alone is rarely diagnostic in case of particular kidney infections such as focal and multifocal acute pyelonephritis, Doppler and power-Doppler (PD) techniques are able to increase its sensitivity. Contrast-enhanced ultrasound (CEUS) further improves the signal-to-noise ratio, thus increasing the diagnostic accuracy of ultrasound in case of renal infectious disease. Recent studies performed on kidney transplant recipients have indeed demonstrated the high sensitivity and specificity of CEUS in diagnosing acute pyelonephritis. Moreover, ultrasonography is a useful diagnostic tool in case of kidney abscesses, emphysematous pyelonephritis, early phases of pyonephrosis, and in the evaluation and monitoring of echinococcal cysts. Ultrasound imaging is less specific in diagnosing xanthogranulomatous pyelonephritis, malacoplakia and renal tuberculosis. Finally, several authors recommend routine ultrasound assessment in HIV patients, given the high incidence of renal complications in this population of patients.

[Vascular complications following kidney transplant: the role of color-Doppler imaging]. / Le complicanze vascolari del rene trapiantato: il ruolo dell'eco-color-Doppler.

The progressive decline in the incidence of graft rejection has made urological, surgical, parenchymal and vascular complications of kidney transplant more frequent. The latter, although accounting for only 5-10% of all post-transplant complications, are a frequent cause of graft loss. Ultrasonography, both in B-mode and with Doppler ultrasound, is an important diagnostic tool in case of clinical conditions which might impair kidney function. Even though ultrasonography is considered fundamental in the diagnosis of parenchymal and surgical complications of the transplanted kidney, its role is not fully understood in case of vascular complications of the graft. The specificity of Doppler ultrasound is very important in case of stenosis of the transplanted renal artery, pseudoaneurysms, arteriovenous fistulas, and thrombosis with complete or partial artery or vein occlusion. Doppler and color determinations present high diagnostic accuracy, which is higher in case of successive measurements performed during the follow-up of the graft. Modern techniques including contrast-enhanced ultrasound increase the diagnostic power of ultrasonography in case of vascular complications of the transplanted kidney, planted kidney.

[Echocardiography in nephrology]. / L'ecocardiografia in nefrologia.

Cardiovascular disease is the main cause of mordibity and mortality in patients with chronic kidney disease (CKD) affected by a series of risk factors (hypertension, anemia, left ventricular hypertrophy, cardiac failure and dyslipidemia). The combined presence of these factors raises the cardiovascular risk in CKD patients considerably compared with that of the general population. Nephrologists can play a role in preventing and treating these risk factors and thereby delaying the development of CKD. In preventing CKD, nephrologists who practice ultrasound techniques should have basic know how of echocardiography so that they can screen CKD patients for early referral to a cardiologist. Echocardiography is a noninvasive ultrasound technique that requires adequately trained doctors to perform it. Nephrologists who practice it need to obtain good training and postgraduate certification of competence in echocardiography. These nephrologists should team up with cardiologists rather than replace them, and at the same time be aware that they possess the basic knowledge to manage cardiovascular disease in CKD patients.

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.

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.

[Amino acid loss during dialysis treatment]. / Perdita di aminoacidi nel corso di terapia emodialitica extracorporea.

Protein-calorie malnutrition is a widespread complication in hemodialysis (HD) patients and is associated with increased mortality. The pathogenesis of malnutrition is multifactorial. Intradialytic amino acid (AA) loss is considered one of the cofactors in the complex mechanisms that lead to malnutrition in HD patients. It has been documented that in each dialysis session there is a 6-8 gram loss of AA into the dialysate, which worsens with the use of high-flux membranes. The intradialytic AA loss is variably compensated by reduction of liver synthesis and increased AA release from muscle stores. In malnourished HD patients the serum AA concentration, especially branched-chain AA (BCAA), is correlated with nutritional status and anorexia, whereas BCAA supplementation improves the nutritional parameters and increases appetite. Further studies are necessary to clarify the role of alterations of AA metabolism in the pathogenesis of malnutrition and the potential beneficial effects of BCAA supplementation or alternative treatments in malnourished patients.

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.

Epidemiology of chronic kidney disease in Italy.

Chronic kidney disease (CKD) is becoming a major public health problem worldwide. In Italy, only scarce and partial national data of prevalence have been obtained, from small-size cohorts in single settings not representative of the general Italian population. In this article, we review in detail the prevalence data obtained by the Gubbio study and the Italian Society of Nephrology - Health Search study, and describe the emerging problem of CKD definition in the elderly.

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 m(2); 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.

[Role of paracalcitol in the management of non-dialysis CKD: state of art and... Unmet needs]. / Ruolo del paracalcitolo nella terapia conservativa della malattia renale cronica: stato dell'arte e... Unmet needs.

Chronic kidney disease (CKD) is associated with a high risk of cardiovascular morbidity and mortality due to the high prevalence of traditional risk factors and the presence of factors specific to CKD. Vitamin D deficiency and secondary hyperparathyroidism are the earliest complications in CKD, and observational data show that low plasma vitamin D is an independent predictor of death in patients with CKD. Oral supplementation with active oral vitamin D appears to be associated with greater survival but a significant improvement in renal outcome has not been demonstrated, probably because of its unwanted side effects (increase in plasma calcium and phosphate levels). Oral paracalcitol, a new vitamin D receptor activator, is now available for CKD patients not yet on dialysis. It suppresses PTH with a low incidence of increased serum calcium and phosphate levels in patients treated with dialysis and when high doses are administered. Furthermore, recent data show that paracalcitol treatment in CKD patients also results in a significant reduction of albuminuria, which is a major risk factor for cardiorenal outcome. The antiproteinuric effect of paracalcitol appears to be the result of intrarenal suppression of the renin-angiotensin system (RAS). Therefore, paracalcitol may be mostly effective in reducing albuminuria in patients already treated with RAS inhibitors who show compensatory increments of RAS components. Studies in large patients series and with adequate follow-up are needed to evaluate the effects of long-term paracalcitol treatment in CKD and its potential role in improving renal outcome in comparison not only with placebo but also other vitamin D metabolites and analogues.