Central Venous Stenosis after Hemodialysis: Case Reports and Relationships to Catheters and Cardiac Implantable Devices.

The appropriate vascular access for hemodialysis in patients with cardiac implantable electronic devices (CIED) is undefined. We describe two cases of end-stage renal disease patients with CIED and tunneled central venous catheter (CVC) who developed venous cava stenosis: (1) a 70-year-old man with sinus node disease and pacemaker in 2013, CVC, and a Brescia-Cimino forearm fistula in 2015; (2) a 75-year-old woman with previous ventricular arrhythmia with implanted defibrillator in 2014 and CVC in 2016. In either case, after about 1 year from CVC insertion, patients developed superior vena cava (SVC) syndrome due to stenosis diagnosed by axial computerized tomography. In case 1, the patient was not treated by angioplasty of SVC and removed CVC with partial resolving of symptoms. In case 2, a percutaneous transluminal angioplasty with placement of a new CVC was required. To analyze these reports in the context of available literature, we systematically reviewed studies that have analyzed the presence of central venous stenosis associated with the simultaneous presence of CIED and CVC. Five studies were found; two indicated an increased incidence of central venous stenosis, while three did not find any association. While more studies are definitely needed, we suggest that these patients may benefit from epicardial cardiac devices and the insertion of devices directly into the ventriculus. If the new devices are unavailable or contraindicated, peritoneal dialysis or intensive conservative treatment in older patients may be proposed as alternative options.

[Hyperuricaemia and Chronic Kidney Disease].

Hyperuricemia is defined as serum uric acid values greater than 6 mg/dl and could occur either due to hyperproduction or as a result of reduced renal excretion, which exceeds gut compensation. In Italy, prevalence is around 12% of the general population and increases in renal disease up to 60%. Recent experimental studies demonstrated a role of uric acid in the development of arterial hypertension and systemic arteriosclerosis, with an increase in cardiovascular risk. It also appears from observational studies that high uric acid is an independent risk factor associated with de novo onset of chronic kidney disease after adjustment of main confounding variables. Hyperuricemic subjects treated with febuxostat, a selective inhibitor of xantino-oxidase, showed in RCTs a better control of hyperuricaemia in comparison with those receiving allopurinol. Moreover, observational studies indicate that urate lowering treatment could be helpful in reducing cardiovascular events as well as in slowing the progression of chronic kidney disease; randomized controlled studies, designed to assess as primary outcome the nephroprotective effect of urate lowering treatment, are in progress.

High-flow arteriovenous fistula and heart failure: could the indexation of blood flow rate and echocardiography have a role in the identification of patients at higher risk?

BACKGROUND: Although only high-flow arteriovenous fistulas (AVFs) are postulated to cause high-output cardiac failure (HOCF), there are currently no universally accepted criteria defining a high-flow fistula. METHODS: To verify if vascular access blood flow (Qa) ≥ 2000 ml/min provides an accurate definition of high-flow fistula, we selected 29 consecutive patients with Qa ≥ 2000 ml/min at color-duplex ultrasound examination and assessed them for the presence of cardiac failure symptoms; transthoracic echocardiography was also performed. RESULTS: Nineteen patients (65%) had heart failure symptoms and were classified with HOCF. At receiver operating characteristic (ROC) curve analysis, Qa ml/min values did not identify patients with heart failure symptoms but when AVF blood flow was indexed for height2.7, Qa ≥ 603 ml/min/m2.7 detected the occurrence of HOCF with good accuracy (sensitivity 100%, specificity 60%, efficiency 86%, positive predictive value 83%, negative predictive value 100%, area under curve 0.75). At echocardiographic evaluation, patients with Qa ≥ 603 ml/min/m2.7 had a more severe increase of left ventricular mass (63 ± 18 vs. 47 ± 7 g/m2.7, p < 0.003), left ventricular diastolic volume (140 ± 42 vs. 109 ± 14 ml, p < 0.007), left atrial volume (53 ± 23 vs. 39 ± 5 ml/m2, p < 0.015), a higher incidence of diastolic dysfunction (70 vs. 17%, p < 0.019) and higher CO reduction after AVF manual compression (2151 ± 875 vs. 1292 ± 527 ml/min, p < 0.009) than patients with Qa < 603 ml/min/m2.7. CONCLUSIONS: Indexation of AVF blood flow should be considered in defining high-flow fistula because the effect of Qa may differ in individuals of different sizes. A Qa value ≥ 603 ml/min/m2.7 and its association with some echocardiographic alterations could identify patients at higher risk for HOCF.

Stage 5-CKD under nephrology care: to dialyze or not to dialyze, that is the question.

Appropriate timing of starting chronic dialysis in patients with advanced chronic kidney disease (CKD) under nephrology care still is undefined. We systematically reviewed the most recent studies that have compared outcomes of stage 5-CKD under conservative versus substitutive treatment. Eleven studies, most in elderly patients, were identified. Results indicate no advantage of dialysis over conservative management in terms of survival, hospitalization or quality of life. This information is integrated with a case report on a middle-aged CKD patient followed in our clinic who has remained for 15 years in stage 5 despite severe disease. The patient is a diabetic woman who underwent right nephrectomy in 1994 because of renal tuberculosis. In 1999, she commenced regular nephrology care in our clinic and, since 2000, when she was 53 years old, her estimated glomerular filtration rate (eGFR) has been ≤15 ml/min/1.73 m(2). Over the last decade, despite, several episodes of acute kidney injury and placement of permanent percutaneous nephrostomy in 2001, renal function has remained remarkably stable, though severely impaired (eGFR 7.7-5.6 ml/min/1.73 m(2)). Our systematic analysis of the literature and this case report highlight the need for further studies, not limited exclusively to elderly patients, to verify the efficacy of non-dialysis treatment in stage 5-CKD patients. Meanwhile, nephrologists may consider that their intervention can safely prolong for several years the dialysis-free condition in ESRD independently of age.

Hypertension and Prehypertension and Prediction of Development of Decreased Estimated GFR in the General Population: A Meta-analysis of Cohort Studies.

BACKGROUND: Whether blood pressure (BP) plays an independent predictive role in the onset of decreased glomerular filtration rate (GFR) remains ill-defined because existing meta-analyses have incorporated data from studies that included individuals with low GFRs at baseline. This question is critical to optimize chronic kidney disease prevention in the general population. STUDY DESIGN: Systematic review and meta-analysis of longitudinal cohort studies. SETTING & POPULATION: Adults from general population. SELECTION CRITERIA FOR STUDIES: We identified in PubMed, EMBASE, and the Cochrane Library database all cohort studies evaluating the role of BP in the incidence of decreased estimated GFR (eGFR; defined as eGFR<60 mL/min/1.73 m2) in individuals without decreased kidney function at baseline. PREDICTORS: Hypertension (BP>140/90 mmHg), prehypertension (systolic BP of 120-139 and/or diastolic BP of 80-89 mmHg), and BP as a continuous variable. OUTCOMES: Risk for decreased eGFR reported as relative risk (RR) and 95% CI. Heterogeneity (I2) was also evaluated. RESULTS: Data from 16 cohorts (315,321 participants) were analyzed. All studies had a Newcastle-Ottawa score in the range of 6 to 8, denoting high quality. During a mean follow-up of 6.5 years, decreased eGFR occurred in 6.6% of participants. The presence of prehypertension and hypertension increased renal risk (RRs of 1.19 [95% CI, 1.07-1.33; I2=23.8%] and 1.76 [95% CI, 1.58-1.97; I2=37.7%], respectively). Similarly, we found that every 10-mm Hg increase in systolic and diastolic BPs associated with higher risk for decreased eGFR (RRs of 1.08 [95% CI, 1.04-1.11; I2=60.0%] and 1.12 [95% CI, 1.04-1.20; I2=51.4%], respectively). Metaregression analysis showed greater risk with older age (P=0.03), whereas other covariates were not significant. LIMITATIONS: No individual patient-level data. CONCLUSIONS: Prehypertension and hypertension, as BP levels, are independent predictors of decreased GFR in the general population, with the effect being more pronounced in the elderly. These findings are important for improving risk stratification in the general population.

Management of CKD-MBD in non-dialysis patients under regular nephrology care: a prospective multicenter study.

BACKGROUND: Knowledge about mineral bone disorder (MBD) management in non-dialysis chronic kidney disease (ND-CKD) patients is scarce, although essential to identifying areas for therapeutic improvement. METHODS: We prospectively evaluated current management of CKD-MBD in two visits, performed 6 months apart, in 727 prevalent ND-CKD stage 3b-5 patients from 19 nephrology clinics. Therapeutic inertia was defined as lack of treatment despite hyperphosphatemia and/or hypocalcemia, and/or hyperparathyroidism. The primary endpoint was the prevalence of achieved target for CKD-MBD parameters and related treatments (phosphate binders, vitamin D and calcium supplements). The secondary endpoint was the assessment of prevalence and clinical correlates of therapeutic inertia. RESULTS: Over 65 % of patients did not reach parathormone (PTH) targets, while 15 and 19 % did not reach phosphate and calcium targets, respectively. The proportion of untreated patients decreased from stage 3b to 5 (at baseline, from 60 to 16 %, respectively). From baseline to the 6-month visit, the achievement of targets remained stable. Low protein diet was prescribed in 26 % of patients, phosphate binders in 17.3 % (calcium-based binders 15.5 %, aluminium binders 1.8 %), and vitamin D in 50.5 %. The overall prevalence of therapeutic inertia at the 6-month visit was 34.0 % (for hyperphosphatemia, 54.3 %). Compared to CKD stage 3, the likelihood of therapeutic inertia was 40 and 68 % lower at stage 4 and 5, respectively. CONCLUSIONS: PTH, calcium and phosphate targets were not reached in a significant proportion of patients. One-third of patients with at least one MBD parameter not-at-target remained untreated. Therapeutic inertia regarding CKD-MBD treatment may be a major barrier to optimizing the prevention and cure of CKD-MBD.

[Anti-diabetics and chronic kidney disease]. / Terapia antidiabetica nel paziente con diabete tipo 2 e malattia renale cronica: "an update".

Diabetes mellitus (DM) is the most important non-communicable disease after hypertension. Prevalence of type 2 DM has progressively increased over the last decades. In Italy, 11.8% of the general adult population can be identified as diabetic. The major complication of DM is diabetic nephropathy (DM-CKD), which develops in approximately one-third of diabetics. Achieving optimal glycemic control is the first therapeutic goal in the management of DM-CKD. In recent years, new antidiabetic drugs have been marketed (GLP1 analogues, DPP-4 inhibitors, SGLT-2 inhibitors) to ameliorate glycemia in patients nave or treated by means of traditional agents, such as sulfonylureas, metformin, glinides, insulin. However, use of these drugs in DM-CKD should be evaluated carefully, mainly because of the higher risk of hypoglycemia that requires dosing adjustments. Metformin still represents an adequate choice if proper dose adjustments are made on the basis of renal function. Sulfonylureas with limited renal clearance, i.e., gliquidone, glipizide and gliclazide are an alternative to metformin and more effective than repaglinide on glycemic control. Other antidiabetic agents with potential nephroprotective effects, namely DPP-4 inhibitors, incretin analogues and SGLT-2 inhibitors, may allow nephroprotective effects independent of glycemic control. Insulin remains the cornerstone of therapy when oral therapy is no longer effective.

[Clinical experience with ferric carboxymaltose in non-dialysis chronic kidney disease]. / Ferro carbossimaltosio nella malattia renale cronica non dialitica: una iniziale esperienza clinica.

BACKGROUND: Patients with non-dialysis-dependent chronic kidney disease (ND-CKD) often show anemia and iron deficiency despite oral iron supplementation caused by poor iron absorption, intolerance and non-compliance. METHODS: We prospectively followed seven adult patients with ND-CKD (eGFR <60 ml/min/1.73m2), anemia (Hb<11 g/dl or treatment with ESA), iron deficiency (TSAT<20% and/or ferritin<100 ng/mL) and intolerant or non-responders to oral iron supplementation. Patients received ferric carboxymaltose (FCM) (single dose of 500 mg iv) eventually followed by further doses if iron deficiency persisted. Hemoglobin, ferritin, TSAT and ESA doses were recorded at baseline and after 2, 4, 8, 12, 16, 20 and 24 weeks. RESULTS: After 2 weeks of FCM, ferritin increased from 5348 to 222154 ng/mL (P<0.05) and remained steady thereafter. The increase of TSAT from baseline (115%) was more gradual being significant from week 4 (198%) up to week 24 (2412%). During the study, patients received on average 2.31.0 injections of FCM, to the amount of 1143440 mg. Hb levels remained stable throughout the study, despite a significant reduction of ESA dosage (from 3426 g/week at baseline to 1116 and 1710 g/week, after 4 and 24 weeks, respectively). On average, the ESA dose saving was 2024 g/week. Even considering the higher cost of FCM, ESA dose reduction allowed shortening overall costs by 673/patient during the 24 weeks of study. CONCLUSION: In ND-CKD patients, FCM is effective in correcting iron deficiency and associated with stable Hb levels and significant decrease of ESA dosage. This allows a marked reduction of costs for anemia correction.

Reassessment of Ambulatory Blood Pressure Improves Renal Risk Stratification in Nondialysis Chronic Kidney Disease: Long-Term Cohort Study.

In nondialysis chronic kidney disease, ambulatory blood pressure (ABP) performs better than clinic BP in predicting outcome, but whether repeated assessment of ABP further refines prognosis remains ill-defined. We recruited 182 consecutive hypertensive patients with nondialysis chronic kidney disease who underwent 2 ABPs 12 months apart to evaluate the enhancement in risk stratification provided by a second ABP obtained 1 year after baseline on the risk (hazard ratio and 95% confidence interval) of composite renal end point (death, chronic dialysis, and estimated glomerular filtration rate decline ≥40%). The difference in daytime and nighttime systolic BP between the 2 ABPs (daytime and nighttime bias) was added to a survival model including baseline ABP. Net reclassification improvement was also calculated. Age was 65.6±13.4 years; 36% had diabetes mellitus and 36% had previous cardiovascular event; estimated glomerular filtration rate was 42.2±19.6 mL/min per 1.73 m(2), and clinic BP was 145±18/80±11 mm Hg. Baseline ABP (daytime, 131±16/75±10 and nighttime, 122±18/66±10 mm Hg) and daytime/nighttime BP goals (58.2% and 43.4%) did not change at month 12. Besides baseline ABP values, bias for daytime and nighttime systolic BP linearly associated with renal outcome (1.12, 1.04-1.21 and 1.18, 1.08-1.29 for every 5-mm Hg increase, respectively). Classification of patients at risk improved when considering nighttime systolic level at second ABP (net reclassification improvement, 0.224; 95% confidence interval, 0.005-0.435). Patients with first and second ABPs above target showed greater renal risk (2.15, 1.29-3.59 and 1.71, 1.07-2.72, for daytime and nighttime, respectively). In nondialysis chronic kidney disease, reassessment of ABP at 1 year further refines renal prognosis; such reassessment should specifically be considered in patients with uncontrolled BP at baseline.

Independent Role of Underlying Kidney Disease on Renal Prognosis of Patients with Chronic Kidney Disease under Nephrology Care.

Primary kidney disease is suggested to affect renal prognosis of CKD patients; however, whether nephrology care modifies this association is unknown. We studied patients with CKD stage I-IV treated in a renal clinic and with established diagnosis of CKD cause to evaluate whether the risk of renal event (composite of end-stage renal disease and eGFR decline ≥ 40%) linked to the specific diagnosis is modified by the achievement or maintenance in the first year of nephrology care of therapeutic goals for hypertension (BP ≤ 130/80 mmHg in patients with proteinuria ≥ 1 50 mg/24h and/or diabetes and ≤ 140/90 in those with proteinuria <150 mg/24h and without diabetes) anemia (hemoglobin, Hb ≥ 11 g/dL), and proteinuria (≤ 0.5 g/24h). Survival analysis started after first year of nephrology care. We studied 729 patients (age 64 ± 15 y; males 59.1%; diabetes 34.7%; cardiovascular disease (CVD) 44.9%; hypertensive nephropathy, HTN 53.8%; glomerulonephritis, GN 17.3%; diabetic nephropathy, DN 15.9%; tubule-interstitial nephropathy, TIN 9.5%; polycystic kidney disease, PKD 3.6%). During first year of Nephrology care, therapy was overall intensified in most patients and prevalence of main therapeutic goals generally improved. During subsequent follow up (median 3.3 years, IQR 1.9-5.1), 163 renal events occurred. Cox analysis disclosed a higher risk for PKD (Hazard Ratio 5.46, 95% Confidence Intervals 2.28-10.6) and DN (1.28,2.99-3.05), versus HTN (reference), independently of age, gender, CVD, BMI, eGFR or CKD stage, use of RAS inhibitors and achievement or maintenance in the first year of nephrology care of each of the three main therapeutic goals. No interaction was found on the risk of CKD progression between diagnostic categories and month-12 eGFR (P=0.737), as with control of BP (P=0.374), Hb (P=0.248) or proteinuria (P=0.590). Therefore, in CKD patients under nephrology care, diagnosis of kidney disease should be considered in conjunction with the main risk factors to refine renal risk stratification.

Nephroprotection with saxagliptin.

The nephroprotective effect of the new anti-diabetic drugs acting on incretin system is suggested by preclinical studies. However, no study evaluating kidney effects of these drugs as primary outcome on the long term has been conducted in patients followed in diabetes centers. We designed a pilot observational study involving two diabetes clinics to evaluate the effect of prolonged treatment with saxagliptin on renal function in type 2 diabetics. Patients were enrolled if treated for at least 12 months with saxagliptin without concurrent changes to anti-hypertensive and lipid-lowering therapy. Primary outcome was to evaluate the effect of saxagliptin on albuminuria and estimated glomerular filtration rate (eGFR). Secondary outcomes were the effects of treatment on common clinical and laboratory parameters. Sixty-three patients were enrolled. After 12 months of treatment with saxagliptin, albuminuria declined from a mean (95%CI) of 39 (25-52) to 22 (14-30) mg/l (P<0.001), and the prevalence of increased albuminuria (>20 mg/L) diminished by 27% versus baseline. The anti-albuminuric effect was independent of glycemic and blood pressure control. The eGFR remained unchanged after treatment in the presence of decreased glycated hemoglobin (from 7.1 to 6.7%). Therefore, this pilot study suggests that saxagliptin treatment in diabetic patients at high renal risk is associated with a reduction in albuminuria and GFR stability. Prospective trials are required to confirm the potential nephroprotective effects of saxagliptin.

[Chronic kidney dysfunction in the elderly patient: physiological process or disease?]. / Disfunzione renale nell'anziano: processo fisiologico o malattia?

The last few years have seen a steady rise in numbers of patients with chronic kidney disease (CKD), mainly because of the increased prevalence of older patients. Today, most new diagnoses of CKD are made in patients belonging to the large subgroup of subjects aged 65 years or over, who often present with mild-to-moderate CKD. Given the recent rise in numbers of elderly CKD patients referred to American renal clinics, the American Society of Nephrology has recently endorsed a study group dedicated to this group of patients, Geriatric Nephrology, with the aim of increasing knowledge on CKD in the elderly and subsequently improving the clinical management of older patients. Indeed, several questions remain open and further studies are required to clarify diagnostic criteria for 'true' CKD in the elderly and the associated 'real' clinical implications in terms of hard outcomes. This review aims to address a hot topic through evaluation of the most recent and influential studies regarding the relationship between ageing and CKD.

[Limitations of blood pressure target in non-dialysis chronic kidney disease: a question of method?]. / Limiti del target pressorio nell'insufficienza renale cronica non-dialitica: una questione di metodo?

International guidelines recommend to reduce blood pressure (BP) levels below 130/80 mmHg in non-dialysis chronic kidney disease (CKD) patients. However, this BP target has not been validated by randomized controlled trials and is mainly driven by data obtained in observational and post-hoc analyses suggesting that it improves the renal and, to some extent, cardiovascular prognosis. The inconclusive results on the prognostic role of the BP target in patients with CKD might also relate to the limited ability of office BP readings to adequately stratify the global risk of this population. In fact, alterations of the pressure profile (such as white-coat hypertension) and nighttime hypertension are common in CKD patients. Recent studies have demonstrated that ambulatory blood pressure monitoring (ABPM) is superior to clinic BP measurements in predicting renal death and cardiovascular events. Therefore, while waiting for the results from the ongoing randomized Systolic Blood Pressure Intervention Trial (SPRINT) comparing the effect on cardiorenal prognosis of two BP target levels, the more widespread use of ABPM is desirable in CKD patients.

[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.

[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.