World Journal of Nephrology最新文献

Aim: To examine whether hemodialysis (HD) patients with restless legs syndrome (RLS) are subjects of greater fatigue and impaired quality of life (QoL) compared to HD patients without RLS.

Methods: Eighty five stable HD patients participated in this study. According to their RLS status, the patients were divided into the RLS group (n = 23) and the non-RLS group (n = 62). QoL, fatigue, sleep quality, daily sleepiness and depression symptoms were assessed by using various questionnaires. Finally, biochemical parameters including iron, ferritin, hemoglobin, hematocrit and parathormone were assessed.

Results: The HD patients with RLS scored worse in all the questionnaires used in the study (P < 0.05). The patients with RLS were more likely to receive the HD therapy on the morning shift, whilst 43.5% of the RLS patients reported to experience the RLS symptoms also during HD. The severity of RLS was correlated with fatigue, depression score and sleep quality (P < 0.05).

Conclusion: HD patients with RLS are subject to lower QoL related parameters and greater fatigue compared to HD patients without RLS. RLS should be successfully managed in order to improve the QoL of the sufferers.

Chronic kidney disease is a prevalent condition that affects millions of people worldwide and is a major risk factor of cardiovascular morbidity and mortality. The main diseases that lead to chronic kidney disease are frequent entities as diabetes mellitus, hypertension and glomerulopathies. One of the clinical markers of kidney disease progression is proteinuria. Moreover, the histological hallmark of kidney disease is sclerosis, located both in the glomerular and in the interstitial compartments. Glomerulosclerosis underscores an irreversible lesion that is clinically accompanied by proteinuria. In this regard, proteinuria and glomerular sclerosis are linked by the cell that has been conserved phylogenetically not only to prevent the loss of proteins in the urine, but also to maintain the health of the glomerular filtration barrier: The podocyte. It can then be concluded that the link between proteinuria, kidney disease progression and chronic kidney disease is mainly related to the podocyte. What is this situation due to? The podocyte is unable to proliferate under normal conditions, and a complex molecular machinery exists to avoid its detachment and eventual loss. When the loss of podocytes in the urine, or podocyturia, is taking place and its glomerular absolute number decreased, glomerulosclerosis is the predominant histological feature in a kidney biopsy. Therefore, tissular podocyte shortage is the cause of proteinuria and chronic kidney disease. In this regard, podocyturia has been demonstrated to precede proteinuria, showing that the clinical management of proteinuria cannot be considered an early intervention. The identification of urinary podocytes could be an additional tool to be considered by nephrologists to assess the activity of glomerulopathies, for follow-up purposes and also to unravel the pathophysiology of podocyte detachment in order to tailor the therapy of glomerular diseases more appropriately.

Aim: To test whether muscle mass evaluated by creatinine excretion (EX_Cr) is maintained in patients with end-stage kidney disease (ESKD) treated by peritoneal dialysis (PD), we evaluated repeated measurements of EX_Cr in a PD population.

Methods: One hundred and sixty-six PD patients (94 male, 72 female) receiving the same PD dose for the duration of the study (up to approximately 2.5 years) had repeated determinations of total (in urine plus spent dialysate) 24-h EX_Cr (EX_Cr T) to assess the adequacy of PD by creatinine clearance. All 166 patients had two EX_Cr T determinations, 84 of the 166 patients had three EX_Cr T determinations and 44 of the 166 patients had four EX_Cr T measurements. EX_Cr T values were compared using the paired t test in the patients who had two studies and by repeated measures ANOVA in those who were studied three or four times.

Results: In patients who were studied twice, with the first and second EX_Cr T measurements performed at 9.2 ± 15.2 mo and 17.4 ± 15.8 mo after onset of PD, respectively, EX_Cr T did not differ between the first and second study. In patients studied three times and whose final assessment occurred 24.7 ± 16.3 mo after initiating PD, EX_Cr T did not differ between the first and second study, but was significantly lower in the third study compared to the first study. In patients who were studied four times and whose fourth measurement was taken 31.9 ± 16.8 mo after onset of PD, EX_Cr T did not differ between any of the studies. The average EX_Cr T value did not change significantly, with the exception of the third study in the patients studied thrice. However, repeated determinations of EX_Cr T in individuals showed substantial variability, with approximately 50% of the repeated determinations being higher or lower than the first determination by 15% or more.

Conclusion: The average value of EX_Cr T remains relatively constant for up to 2.5 years of follow-up in PD patients who adhere to the same PD schedule. However, repeated individual EX_Cr T values vary considerably in a large proportion of the patients. Further studies are needed to evaluate the clinical significance of varying EX_Cr T values and the stability of EX_Cr T beyond 2.5 years of PD follow-up.

Cyclophosphamide is frequently used to treat cancer, autoimmune and renal diseases, such as rapidly progressive glomerulonephritis. Its side effects are well-known, including bone marrow depression, infections, alopecia, sterility, bladder malignancy and hemorrhagic cystitis. Moreover, in some cases cyclophosphamide use has been related to the onset of hyponatremia, by development of a syndrome of inappropriate antidiuresis. Indeed, severe hyponatremia has been previously reported in patients treated with high-dose or moderate-dose of intravenous cyclophosphamide, while only few cases have been reported in patients treated with low dose. Here, we discuss a case of a syndrome of inappropriate antidiuresis followed to a single low-dose of intravenous cyclophosphamide in a patient with a histological diagnosis of acute glomerulonephritis, presenting as acute kidney injury. After cyclophosphamide administration (500 mg IV), while renal function gradually improved, the patient developed confusion and headache. Laboratory examinations showed serum sodium concentration dropped to 122 mmol per liter associated with an elevated urinary osmolality of 199 mOsm/kg, while common causes of acute hyponatremia were excluded. He was successfully treated with water restriction and hypertonic saline solution infusion with the resolution of the electrolyte disorder. This case, together with the previous ones already reported, highlights that electrolyte profile should be strictly monitored in patients undergoing cyclophosphamide therapy in order to early recognize the potentially life-threatening complications of acute water retention.

Congestion is an integral component of cardiorenal syndrome and portends an adverse impact on the outcomes. Recent studies suggest that congestion has the ability of modulating the interactions between the kidney and the heart in this setting. Peritoneal dialysis (PD) is a home-based therapeutic modality that is not only offered to patients with end-stage renal disease to provide solute clearance and ultrafiltration, but it has also been used in patients with refractory heart failure and fluid overload to help optimize volume status. Several uncontrolled studies and case series have so far evaluated the role of PD in management of hypervolemia for patients with heart failure. They have generally reported favorable results in this setting. However, the data on the outcomes of patients with end-stage renal disease and concomitant heart failure is mixed, and the proposed theoretical advantages of PD might not translate into improved clinical endpoints. Congestion is prevalent in this patient population and has a significant effect on their survival. As studies suggest that a significant subset of patients with end-stage renal disease who receive PD therapy are hypervolemic, suboptimal management of congestion could at least in part explain these conflicting results. PD is a highly flexible therapeutic modality and the choice of techniques, regimens, and solutions can affect its ability for optimization of fluid status. This article provides an overview of the currently available data on the role and clinical relevance of congestion in patients with cardiorenal syndrome and reviews potential options to enhance decongestion in these patients.

Aim: To investigate the relationship between circadian variations in blood pressure (BP) and albuminuria at rest, and during exercise in non-hypertensive type 2 diabetes (T2D) patients.

Methods: We conducted a cross-sectional study in well controlled T2D patients, non-hypertensive, without clinical proteinuria and normal creatinine clearance. In each participant, we recorded the BP using ambulatory blood pressure monitoring (ABPM) for 24-h, and albuminuria at rest and after a standardized treadmill exercise.

Results: We enrolled 27 type 2 patients with a median age of 52; and a mean duration of diabetes and HbA1c of 3.6 ± 0.8 years and 6.3% ± 0.5% respectively. Using a 24-h ABPM, we recorded a mean diurnal systolic blood pressure (SBP) of 128 ± 17 mmHg vs nocturnal of 123 ± 19 mmHg (P = 0.004), and mean diurnal diastolic blood pressure (DBP) of 83 ± 11 mmHg vs nocturnal 78 ± 14 mmHg (P = 0.002). There was a significant difference between albuminuria at rest [median = 23 mg, interquartile range (IQR) = 10-51] and after exercise (median = 35 mg, IQR = 23-80, P < 0.001). Patients with exercise induced albuminuria had an increase in nocturnal BP values on all three components (128 mmHg vs 110 mmHg, P = 0.03 for SBP; 83 mmHg vs 66 mmHg, P = 0.04; 106 vs 83, P = 0.02 for mean arterial pressure), as well as albuminuric patients at rest. Moreover, exercise induced albuminuria detect a less increase in nocturnal DBP (83 vs 86, P = 0.03) than resting albuminuria.

Conclusion: Exercise induced albuminuria is associated with an increase in nocturnal BP values in T2D patients.

Our meta-analysis published in 2010 provided evidence that low levels of serum albumin (hypoalbuminemia) are a significant independent predictor of acute kidney injury (AKI) and death following AKI. Since then, a large volume of additional data from observational clinical studies has been published further evaluating the relationship between serum albumin and AKI occurrence. This is an updated review of the literature to re-evaluate the hypothesis that hypoalbuminemia is independently associated with increased AKI risk. Eligible studies published from September 2009 to December 2016 were sought in PubMed (MEDLINE) and forty-three were retained, the great majority being retrospective observational cohort studies. These included a total of about 68000 subjects across a diverse range of settings, predominantly cardiac surgery and acute coronary interventions, infectious diseases, transplant surgery, and cancer. Appraisal of this latest data set served to conclusively corroborate and confirm our earlier hypothesis that lower serum albumin is an independent predictor both of AKI and death after AKI, across a range of clinical scenarios. The body of evidence indicates that hypoalbuminemia may causally contribute to development of AKI. Furthermore, administration of human albumin solution has the potential to prevent AKI; a randomized, controlled study provides evidence that correcting hypoalbuminemia may be renal-protective. Therefore, measurement of serum albumin to diagnose hypoalbuminemia may help identify high-risk patients who may benefit from treatment with exogenous human albumin. Multi-center, prospective, randomized, interventional studies are warranted, along with basic research to define the mechanisms through which albumin affords nephroprotection.

Aim: To investigate the therapeutic potential of tesevatinib (TSV), a unique multi-kinase inhibitor currently in Phase II clinical trials for autosomal dominant polycystic kidney disease (ADPKD), in well-defined rodent models of autosomal recessive polycystic kidney disease (ARPKD).

Methods: We administered TSV in daily doses of 7.5 and 15 mg/kg per day by I.P. to the well characterized bpk model of polycystic kidney disease starting at postnatal day (PN) 4 through PN21 to assess efficacy and toxicity in neonatal mice during postnatal development and still undergoing renal maturation. We administered TSV by oral gavage in the same doses to the orthologous PCK model (from PN30 to PN90) to assess efficacy and toxicity in animals where developmental processes are complete. The following parameters were assessed: Body weight, total kidney weight; kidney weight to body weight ratios; and morphometric determination of a cystic index and a measure of hepatic disease. Renal function was assessed by: Serum BUN; creatinine; and a 12 h urinary concentrating ability. Validation of reported targets including the level of angiogenesis and inhibition of angiogenesis (active VEGFR2/KDR) was assessed by Western analysis.

Results: This study demonstrates that: (1) in vivo pharmacological inhibition of multiple kinase cascades with TSV reduced phosphorylation of key mediators of cystogenesis: EGFR, ErbB2, c-Src and KDR; and (2) this reduction of kinase activity resulted in significant reduction of renal and biliary disease in both bpk and PCK models of ARPKD. The amelioration of disease by TSV was not associated with any apparent toxicity.

Conclusion: The data supports the hypothesis that this multi-kinase inhibitor TSV may provide an effective clinical therapy for human ARPKD.

Contrast-induced acute kidney injury (CI-AKI) is one of the most common causes of AKI in clinical practice. CI-AKI has been found to be strongly associated with morbidity and mortality of the patients. Furthermore, CI-AKI may not be always reversible and it may be associated with the development of chronic kidney disease. Pathophysiology of CI-AKI is not exactly understood and there is no consensus on the preventive strategies. CI-AKI is an active research area thus clinicians should be updated periodically about this topic. In this review, we aimed to discuss the indications of contrast-enhanced imaging, types of contrast media and their impact on nephrotoxicity, major pathophysiological mechanisms, risk factors and preventive strategies of CI-AKI and alternative non-contrast-enhanced imaging methods.

Long-term exposure to bioincompatible peritoneal dialysis (PD) solutions frequently results in peritoneal fibrosis and ultrafiltration failure, which limits the life-long use of and leads to the cessation of PD therapy. Therefore, it is important to elucidate the pathogenesis of peritoneal fibrosis in order to design therapeutic strategies to prevent its occurrence. Peritoneal fibrosis is associated with a chronic inflammatory status as well as an elevated oxidative stress (OS) status. Beyond uremia per se, OS also results from chronic exposure to high glucose load, glucose degradation products, advanced glycation end products, and hypertonic stress. Therapy targeting the cannabinoid (CB) signaling pathway has been reported in several chronic inflammatory diseases with elevated OS. We recently reported that the intra-peritoneal administration of CB receptor ligands, including CB₁ receptor antagonists and CB₂ receptor agonists, ameliorated dialysis-related peritoneal fibrosis. As targeting the CB signaling pathway has been reported to be beneficial in attenuating the processes of several chronic inflammatory diseases, we reviewed the interaction among the cannabinoid system, inflammation, and OS, through which clinicians ultimately aim to prolong the peritoneal survival of PD patients.