Thrombophilia in hemodialysis patients: Transfer to peritoneal dialysis is life saving.

The majority of vascular access thrombosis episodes in hemodialysis patients are due to anatomic abnormalities. Thrombophilias are inherited, acquired or mixed disorders which also predispose to venous thromboembolism. They include protein C, protein S and antithrombin deficiencies, as well as gene mutations for prothrombin and factor V Leiden. The most important of the mixed cases is hyperhomocysteinemia, which includes both a genetic and an acquired substrate. We report two patients undergoing hemodialysis who suffered from multiple thrombotic events, the first due to factor V Leiden heterozygosity and the second because of hyperhomocysteinemia due to homozygosity for MTHFR C677T mutation. As no site for vascular access was left, transfer to peritoneal dialysis for both patients improved solute clearance and quality of life with no additional thrombotic events noted.

The Association of dp-ucMGP with Cardiovascular Morbidity and Decreased Renal Function in Diabetic Chronic Kidney Disease.

We aimed to investigate the possible association of the inactive, dephosphorylated, uncarboxylated matrix Gla protein (dp-ucMGP) with oxidized low-density lipoprotein (ox-LDL) and all-cause/cardiovascular (CV) mortality and renal function in diabetic chronic kidney disease (CKD). Ox-LDL and dp-ucMGP were determined in 66 diabetic CKD patients. All patients were prospectively followed for seven years, or until the occurrence of death, or a composite renal outcome of 30% estimated glomerular filtration rate (eGFR) reduction or progression to end-stage renal disease (ESRD) requiring dialysis occurred. Secondary outcomes were the occurrence of CV events. Kaplan-Meier curves showed that patients with plasma dp-ucMGP levels above the median (≥656 pM) had a significantly higher risk for all study endpoints. After adjustment for several well-known cofounders, multivariate Cox analysis showed that high plasma dp-ucMGP levels were associated with all-cause mortality (Hazard ratio-HR = 2.63, 95% Confidence Interval-CI = 1.17-5.94, p = 0.02), CV mortality (HR = 2.82, 95% CI = 1.07-7.49, p = 0.037) and progression of CKD (HR = 4.02, 95% CI = 1.20-13.46, p = 0.024). Circulating dp-ucMGP is associated with mortality and decreased renal function in diabetic CKD.

Can dialysis modality influence quality of life in chronic hemodialysis patients? Low-flux hemodialysis versus high-flux hemodiafiltration: a cross-over study.

BACKGROUND: Hemodiafiltration with online preparation of the substitution [online high-flux hemodiafiltration (OHDF)] and hemodiafiltration with prepared bags of substitution (HDF) are important, recently widely used renal replacement therapies in patients with end-stage renal disease. However, there is little information on the comparative impacts of these modalities versus conventional low-flux hemodialysis (HD) on the quality of life (QoL) of HD patients. This study investigates the effect of dialysis modality on QoL in chronic HD patients. METHODS: In this prospective, randomized, cross-over, open label study, 24 patients were enrolled. Their age were 62 ± 13.34 years (mean ± SD), with the duration of dialysis of 31 ± 23.28 months (mean ± SD). Five of the patients were women. QoL was measured by the Short-Form Health Survey with 36 questions (SF-36) and subscale scores were calculated. Each patient received HD, OHDF, and HDF for 3 months, with the dialysis modality subsequently being altered. They completed the questionnaire of QoL at the end of each period. RESULTS: There were statistical significant differences in QoL for the total SF-36 [36.1 (26.7-45.7) and 40.7 (30.2-62.8)], for classic low-flux HD and high-flux hemodiafiltration, for bodily pain [45 (26.9-66.9) and 55 (35.6-87.5)], and for role limitations due to emotional functioning [0 (0-33.3) and 33.3 (0-100)], respectively. The scores did not differ significantly between the two types of hemodiafiltration. CONCLUSIONS: Our study indicates that QoL differs significantly among patients receiving low-flux HD and high-flux hemodiafiltration, on total SF-36, bodily pain, and role limitations due to emotional functioning. Convective modalities may offer better QoL than diffusive HD.

N-Acetylcysteine: more than preventing contrast-induced nephropathy in uremic patients-focus on the antioxidant and anti-inflammatory properties.

Oxidative stress (OS) has been recognized as a pathophysiologic mechanism underlying the development and progression of chronic kidney disease (CKD). OS, which results from the disturbance of balance among pro-oxidants and antioxidants favoring the pro-oxidants, is present even in early CKD and increases progressively along with deterioration of kidney function to end-stage kidney disease (ESKD). In ESKD, OS is further exacerbated mainly due to dialysis procedures per se and predisposes to increased cardiovascular morbidity and mortality. Therefore, since OS plays a pivotal role in the pathogenesis and progression of atherosclerosis in uremic patients, several strategies aiming to ameliorate OS in these patients have been proposed. Among those, N-acetylcysteine (NAC), a thiol-containing antioxidant agent, has attracted special attention due to its pleiotropic functions and beneficial effect in various OS-related entities including paracetamol overdose and prevention of contrast-induced nephropathy. In this review, we present the currently available literature on the antioxidant and anti-inflammatory properties of NAC in CKD, including hemodialysis and peritoneal dialysis.

Evidence for Cardiorenal Protection with SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Patients with Diabetic Kidney Disease.

For almost two decades, the management of patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) was based on the optimal glycemic and blood pressure control as well as on the adequate blockade of the renin-angiotensin-system. Over the past few years, sodium-glucose co-transporter 2 (SGLT-2) inhibitors and glucagone-like peptide 1 receptor agonists (GLP1-RAs) were added to our therapeutic armarhatum, offering promise for more effective mitigation of the substantial residual cardiorenal risk of these patients. Large randomized controlled trials (RCTs) designed to demonstrate the cardiovascular safety of SGLT-2 inhibitors and GLP1-RAs showed that these novel anti-diabetic medications improve cardiovascular outcomes in patients with T2DM. RCTs conducted specifically in CKD patients with or without T2DM demonstrated that SGLT-2 inhibitors were also effective in retarding the progression of kidney injury to end-stage kidney disease. The kidney protective effects of GLP1-RA are not yet proven, but RCTs are currently ongoing to investigate this crucial research question. In this article, we review the available clinical-trial evidence supporting the use of SGLT-2 inhibitors and GLP1-RAs for cardiorenal protection in patients with T2DM and CKD. We provide clinical practice recommendations for a personalized approach in the use of these novel therapies, according to the severity of CKD and the presence of other cardiometabolic risk factors.

Feeding during Dialysis Increases Intradialytic Blood Pressure Variability and Reduces Dialysis Adequacy.

Whether hemodialysis patients should be allowed or even encouraged to eat during dialysis remains a controversial topic. This cross-over study aimed to evaluate the impact of feeding during dialysis on intradialytic blood pressure (BP) profile and dialysis adequacy in 26 patients receiving thrice-weekly, in-center hemodialysis. Over three consecutive mid-week dialysis sessions, intradialytic BP was monitored using the Mobil-O-Graph device (IEM, Stolberg, Germany). Blood samples were also obtained for the determination of the urea reduction ratio (URR). At baseline, patients underwent dialysis without the provision of a meal. In phases A and B, a meal with either high-protein (1.5 gr/kg of body weight) or low-protein (0.7 gr/kg of body weight) content was administered 1 h after the initiation of dialysis. The sequence of meals (high-protein and low-protein or vice versa) was randomized. Average intradialytic systolic BP (SBP) was similar on all three occasions. However, compared with baseline, the standard deviation (SD) (11.7 ± 4.1 vs. 15.6 ± 7.6 mmHg, p < 0.01), coefficient of variation (CV) (9.5 ± 3.7% vs. 12.4 ± 6.0%, p < 0.01) and average real variability (ARV) (9.4 ± 3.9 vs. 12.1 ± 5.2 mmHg, p < 0.01) of intradialytic SBP were higher in phase A. Similarly, compared with the baseline evaluation, all three indices of intradialytic SBP variability were higher in phase B (SD: 11.7 ± 4.1 vs. 14.1 ± 4.5 mmHg, p < 0.05; CV: 9.5 ± 3.7% vs. 11.1 ± 3.8%, p < 0.05; ARV: 9.4 ± 3.9 vs. 10.9 ± 3.9 mmHg, p < 0.05). Compared with dialysis without a meal, the consumption of a high-protein or low-protein meal resulted in a lower URR (73.4 ± 4.3% vs. 65.7 ± 10.7%, p < 0.001 in phase A and 73.4 ± 4.3% vs. 67.6 ± 4.3%, p < 0.001 in phase B, respectively). In conclusion, in the present study, feeding during dialysis was associated with higher intradialytic SBP variability and reduced adequacy of the delivered dialysis.

Prevalence of Apparent Treatment-Resistant Hypertension in ESKD Patients Receiving Peritoneal Dialysis.

BACKGROUND: Apparent treatment-resistant hypertension (aTRH) is defined as failure to achieve adequate blood pressure (BP) control despite taking ≥3 antihypertensive medications from different categories or when taking ≥4 antihypertensives regardless of BP levels. METHODS: In this cross-sectional study, we estimated the prevalence of aTRH in 140 patients receiving long-term peritoneal dialysis (PD) in four centers of Northern Greece, using the "gold-standard" method of ambulatory BP monitoring for the assessment of BP control status. The presence of subclinical overhydration was evaluated with the method of bioimpedance spectroscopy (BIS). RESULTS: Incorporating the diagnostic threshold of 130/80 mmHg for 24-hour ambulatory BP, the prevalence of aTRH in the overall study population was 30%. Compared to patients without aTRH, those with aTRH tended to be older in age, had higher PD vintage, had higher dialysate-to-plasma creatinine ratio, had more commonly history of diabetes mellitus, and were more commonly current smokers. With respect to the volume status, the overhydration index in BIS was higher in those with versus without aTRH (2.0 ±â€…1.9 L vs. 1.1 ±â€…2.0 L, P < 0.05). The prevalence of volume overload, defined as an overhydration index in BIS > 2.5 L, was also higher in the subgroup of patients with aTRH (38.1% vs. 18.4, P = 0.01). CONCLUSION: The present study showed that among patients on PD, the prevalence of aTRH was 30%. However, 38% of PD patients with aTRH had subclinical overhydration in BIS, suggesting that the achievement of adequate volume control may be a therapeutic opportunity to improve the management of hypertension in this high-risk patient population.The present study showed that among patients on PD, the prevalence of aTRH was 30%. However, 38% of PD patients with aTRH had subclinical overhydration in BIS, suggesting that the achievement of adequate volume control may be a therapeutic opportunity to improve the management of hypertension in this high-risk patient population. CLINICAL TRIALS REGISTRATION: Trial Number NCT03607747.

APD or CAPD: one glove does not fit all.

The use of Automated Peritoneal Dialysis (APD) in its various forms has increased over the past few years mainly in developed countries. This could be attributed to improved cycler design, apparent lifestyle benefits and the ability to achieve adequacy and ultrafiltration targets. However, the dilemma of choosing the superior modality between APD and Continuous Ambulatory Peritoneal Dialysis (CAPD) has not yet been resolved. When it comes to fast transporters and assisted PD, APD is certainly considered the most suitable Peritoneal Dialysis (PD) modality. Improved patients' compliance, lower intraperitoneal pressure and possibly lower incidence of peritonitis have been also associated with APD. However, concerns regarding increased cost, a more rapid decline in residual renal function, inadequate sodium removal and disturbed sleep are APD's setbacks. Besides APD superiority over CAPD in fast transporters, the other medical advantages of APD still remain controversial. In any case, APD should be readily available for all patients starting PD and the most important indication for its implementation remains patient's choice.

Red Blood Cell Distribution Width Is Associated with Deterioration of Renal Function and Cardiovascular Morbidity and Mortality in Patients with Diabetic Kidney Disease.

We sought to investigate the possible association between Red Blood Cell Distribution Width (RDW), vascular calcification, oxidative stress and renal function and all-cause/cardiovascular (CV) mortality, CV events and progression of kidney disease in a cohort of patients with Diabetic Kidney Disease (DKD). Carotid intima media thickness (cIMT) and oxidized low-density cholesterol were measured in 104 Type 2 Diabetes Mellitus (T2DM) patients with established DKD, distributed in all five stages of kidney disease and 38 diabetics with normal renal function. All patients were followed for 7 years with end-points all-cause and CV mortality, CV events and progression to End-Stage Renal Disease (ESRD). RDW was positively correlated with diabetes duration (r = 0.19, p = 0.023) and albuminuria (r = 0.29, p = 0.002). Multivariate regression analysis revealed that RDW was a strong, independent predictor of cIMT value (ß = 0.031, p = 0.012). Kaplan-Meier curves and Cox proportional hazard models revealed that after adjustment for several cofounders, RDW was a significant and independent predictor for all-cause mortality, CV mortality, CV event and progression to ESRD (HR 1.75, p = 0.001, HR 2.03, p = 0.001, HR = 1.66, p < 0.0001 and HR 2.14, p = 0.001 respectively). RDW predicts mortality, CV events and deterioration of renal function in DKD, probably reflecting atherosclerosis.

Osteoporosis after renal transplantation.

Bone loss and fracture are serious sequelae of kidney transplantation, associated with morbidity, mortality and high economic costs. The pathogenesis of post-transplantation bone loss is multifactorial and complex. Pre-existing bone mineral disease is responsible for a significant part, but it is aggravated by risk factors emerging after renal transplantation with immunosuppressive agents being one of the key contributors. The decrease in bone mass is particularly prominent during the first 6-12 months after transplantation, continuing at a lower rate thereafter. Bone mineral density measurements do not predict bone histology and bone biopsy findings reveal heterogeneous lesions, which vary according to time after transplantation. Currently, vitamin D and bisphosphonates are the most extensively tested therapeutic agents against this accelerated bone loss in renal transplant recipients. Both of these agents have proven effective, but there is no evidence that they decrease fracture risk. More studies are needed to examine the complex pathophysiologic mechanisms implicated in this population, as well as the effects of different therapeutic interventions on bone disorders after kidney transplantation.

Improvements in the Management of Diabetic Nephropathy.

The burden of diabetes mellitus is relentlessly increasing. Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide and a major cause of morbidity and mortality in patients with diabetes. The current standard therapy of diabetic nephropathy involves intensive treatment of hyperglycemia and strict blood pressure control, mainly via blockade of the renin-angiotensin system (RAS). Attention has been drawn to additional beneficial effects of oral hypoglycemic drugs and fibrates on other aspects of diabetic nephropathy. On the other hand, antiproteinuric effects of RAS combination therapy do not seem to enhance the prevention of renal disease progression, and it has been associated with an increased rate of serious adverse events. Novel agents, such as bardoxolone methyl, pentoxifylline, inhibitors of protein kinase C (PKC), sulodexide, pirfenidone, endothelin receptor antagonists, vitamin D supplements, and phosphate binders have been associated with controversial outcomes or significant side effects. Although new insights into the pathogenetic mechanisms have opened new horizons towards novel interventions, there is still a long way to go in the field of DN research. The aim of this review is to highlight the recent progress made in the field of diabetes management based on the existing evidence. The article also discusses novel targets of therapy, with a special focus on the major pathophysiologic mechanisms implicated in the initiation and progression of diabetic nephropathy.

Intraocular pressure changes during hemodialysis.

The response of intraocular pressure (IOP) to hemodialysis procedure has been a subject of research throughout many decades. Several studies that evaluated the impact of hemodialysis (HD) on IOP have reported conflicting results and have drawn varied conclusions. Some studies have described an IOP elevation during HD, a finding they attributed to the osmotic disequilibrium between serum and aqueous humor induced by the HD procedure, especially when the facility of the outflow system is already compromised. On the other hand, several studies have reported a significant IOP decrease during HD. The majority of these studies supported the notion that the increase in plasma colloid pressure induced by fluid removal during the HD session is the underlying cause of decreased IOP. Finally, recent investigations did not establish a significant change in IOP measurements during HD. They have therefore suggested that improved dialysis techniques, such as high-flux HD, or hemofiltration and better urea control, maintain better osmolar balance and prevent a marked IOP elevation. Nevertheless, specific preventive measures are still necessary in HD patients with ocular pathologies (e.g., glaucoma) whose vision may be adversely influenced by significant IOP fluctuation.

Animal models in peritoneal dialysis.

Peritoneal dialysis (PD) has been extensively used over the past years as a method of kidney replacement therapy for patients with end stage renal disease (ESRD). In an attempt to better understand the properties of the peritoneal membrane and the mechanisms involved in major complications associated with PD, such as inflammation, peritonitis and peritoneal injury, both in vivo and ex vivo animal models have been used. The aim of the present review is to briefly describe the animal models that have been used, and comment on the main problems encountered while working with these models. Moreover, the differences characterizing these animal models, as well as, the differences with humans are highlighted. Finally, it is suggested that the use of standardized protocols is a necessity in order to take full advantage of animal models, extrapolate their results in humans, overcome the problems related to PD and help promote its use.

Vascular access for hemodialysis: postoperative evaluation and function monitoring.

Vascular access (VA) survival is a crucial issue associated with morbidity and mortality of patients undergoing maintenance hemodialysis. The development of stenosis is the major factor that leads to VA failure. Strategies for early detection of lesions within a VA system before serious complications arise are therefore crucial. The implementation of a VA surveillance program could lead to timely detection of VA dysfunction and referral for correction, reduction in central venous catheter use and decrease in hospitalization and VA-related cost. Suggested methods for arteriovenous fistulae and grafts surveillance include blood flow measurement, static pressure evaluation and duplex ultrasonography. Physical examination is an accepted method in contrast to nonstandardized dynamic pressure measurement for grafts. Access recirculation (not urea based) and dynamic pressure measurements are accepted methods for fistulae. Decreasing URR or Kt/V (otherwise unexplained) and increased (negative) arterial pressure in the dialysis machine are methods of limited sensitivity and specificity for both fistulae and grafts. Measurement of access blood flow has been proposed as the gold standard for the screening of all types of VA. Access flow can be measured by various techniques which are direct or indirect. Several studies about VA surveillance programs have demonstrated conflicting results. Larger, randomized controlled trials need to be carried out in order to clarify whether surveillance programs are necessary and which is the best surveillance strategy for each type of VA.

Sternal instability in a hemodialysis patient with secondary hyperparathyroidism.

A 77-year-old man, 11 years under chronic hemodialysis treatment for chronic renal failure of unknown origin, presented with anterior chest pain, dyspnea with paradoxical breathing, and sternal instability after a simple fall from a standing height. Patient underwent three-vessel coronary artery bypass grafting 31 months ago. Computed tomography with three-dimensional volume rendering showed sternal nonunion with a great gap between the two halves of the sternum and at least one fracture in the left half of the sternum. A successful surgical repair followed. Patient suffered from severe secondary hyperparathyroidism for many years. Despite treatment with sevelamer, paricalcitol and cinacalcet, intact parathyroid hormone was 1682 pg/mL. During the last 5 years, serum intact parathyroid hormone remained steadily above 1000 pg/mL. Patient refused parathyroidectomy in the past. We assume that long-lasting severe hyperparathyroidism contributed to this rare and life-threatening complication of median sternotomy in our patient, due to the detrimental effect of hyperparathyroidism on bone metabolism and its association with increased incidence of bone fractures and defect in bone fracture healing.

Late onset of clinically apparent central vein stenosis due to previous central venous catheter in a patient with inherited thrombophilia.

We describe a case of a patient with a functional kidney transplant who was admitted to our department with clinically evident central vein stenosis (CVS) 7 years after the removal of a central venous catheter (CVC) from the right internal jugular vein. The catheter was used as a hemodialysis access for a 2-month period. In the interval before his last admission, the patient suffered two episodes of deep vein thrombosis. Investigation revealed heterozygosity for factor V Leiden, the most common inherited thrombophilia encountered in 5% of Caucasians, and anticoagulation treatment was started. Magnetic resonance angiography showed stenosis just after the convergence of the right subclavian vein with the internal jugular vein to the innominate vein. Transluminal angioplasty restored venous patency and right upper arm edema resolved. Coexistence of CVS, accompanied by hemodynamic changes and endothelial dysfunction, with thrombophilia fulfill all the elements of the Virchow's triad. Therefore, the patient was at great risk for central vein thrombosis, from which he was possibly protected by the early administration of anticoagulant treatment. This case indicates that CVS can be asymptomatic for several years after CVC removal and also raises the question if thrombophilia workup and investigation for CVS may be beneficial in every patient with CVC placement in order to avoid any harmful outcomes.

The kidney in space.

Renal adaptation in space has been studied during various space missions since the early 70s. Technical and financial disadvantages of performing experiments under real microgravity conditions have warranted the conductance of relative studies under simulated weightlessness on earth. Arriving in microgravity leads to a redistribution of body fluids to the upper part of the body and an exaggerated extravasation very early in-flight. Plasma volume as well as skin evaporation and oral hydration are reduced, while total body water seems to remain stable. Urinary sodium is diminished and a substantial amount of sodium is retained outside the intravascular space. Glomerular filtration rate shows a transient mild increase. Urinary albumin excretion is reduced although initial studies had demonstrated the opposite. Examination of renal histopathology after exposure to simulated microgravity in rats revealed glomerular atrophy, interstitial edema, and degeneration of renal tubular cells. Acute urinary retention which has been reported during spaceflights can lead to certain medical complications that could compromise an entire mission. Kidney stone formation is another important potential hazard for any manned spaceflight. Increased kidney stone formation in space is attributed to several factors including reduced fluid intake, hypercalciuria, and the presence of nanobacteria. Nutritional and pharmacological interventions are currently recommended as preventive measures against renal stone formation in space travelers.

Peritoneal dialysis-related infections recommendations: 2010 update. What is new?

The International Society of Peritoneal Dialysis (ISPD) 2010 guidelines on PD-related infections reflect the bulk of knowledge acquired over the last 5 years. It includes new information about causative agents of peritonitis, isolation techniques, or therapeutic regimens. Monitoring of infection rates by reporting of peritonitis and exit site infections, isolated microorganism, and presumed etiology is recommended. Furthermore, special focus is given on careful evaluation of each episode of peritonitis in order to determine the route of infection and to reassess patient's training. In this article, we record the changes in the last ISPD (2010) guidelines compared to the previous ones published in March 2005.

Adaptation of renal function in heart failure.

Congestive heart failure is the only major cardiovascular disease with an increasing incidence and prevalence in industrialized countries. Despite considerable progress in the clinical management of heart failure during the last 20 years, the prognosis is still worse than in many common types of cancer. The kidney is the main organ affected when cardiac function is compromised. In addition, the kidney significantly contributes to the development of the clinical syndrome of heart failure. Specific hemodynamic and neurohormonal abnormalities define the pathophysiology, clinical presentation, and prognosis of this disorder. In this setting, the kidney plays a dual role: the activation of the renin-angiotensin-aldosterone system and the regulation of sodium and water excretion. The kidney is generally intact in heart failure, but extrarenal stimuli alter its function to a point where mechanisms that are initially homeostatic become maladaptive. In this review article, the mechanisms involved in renal adaptation to heart failure are presented.