Journal of Nephrology

Meijer, Esther; de Jong, Paul E.; Peters, Dorien J.; Gansevoort, Ronald T.

doi: 10.1093/joneph/21.2.133pmid: N/A

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders. It accounts for 6% of the incidence of end-stage renal disease in Europe. Over the last decade, knowledge of the pathology underlying this disease has increased rapidly. Attributing important roles to tubular cell ciliary functioning, cell proliferation and fluid secretion, subsequent alterations in levels of intracellular calcium, adenosine 3’,5’-cyclic monophosphate (cAMP) and activation of a variety of cellular kinases, including mammalian target of rapamycin (mTOR), has laid out the foundations for development of potentially effective treatments. In this editorial, the possible therapeutic roles for vasopressin antagonists, rapamycin, somatostatin and roscovitine are discussed. Clinical trials have been started to investigate the efficacy and safety of these agents for treating ADPKD in humans.

Quinn, Robert R.; Austin, Peter C.; Oliver, Matthew J.

doi: 10.1093/joneph/21.2.139pmid: N/A

The incidence and prevalence of end-stage renal disease (ESRD) continues to rise. While transplantation is the preferred therapy for kidney failure, there is a shortage of donor organs, and the majority of patients will be treated with either peritoneal dialysis (PD) or hemodialysis (HD). Randomized controlled trials comparing patient outcomes on PD and HD are not likely to be successful, as individuals who are educated about their treatment options generally develop a strong preference for one therapy over the other and will not consent to randomization. As a result, prospective cohort studies are frequently the strongest study design available to compare outcomes between dialysis modalities. Previous studies have provided important insights into the relative merits of the 2 therapies. However, they have examined outcomes in relatively heterogeneous groups of ESRD patients and are generally not designed in a manner that mirrors clinical decision-making. We explore several key methodological challenges in the design of observational research in ESRD with a focus on minimizing selection bias and making studies more relevant to the practicing nephrologist. We emphasize that incident patients are preferred in most comparative studies of dialysis modalities. We argue that analyses comparing the outcomes of renal replacement therapy (RRT) modalities should include patients eligible for the therapies being compared and that the way that patients are assigned to treatment groups should reflect decision-making in clinical practice. Finally, the point at which baseline characteristics are measured and we begin tracking patients for the occurrence of outcomes should be chosen carefully.

Vanholder, Raymond; Laecke, Steven Van; Glorieux, Griet

doi: 10.1093/joneph/21.2.146pmid: N/A

The present review gives an overview of the known and newly detected middle molecules and their biological potential. Since many middle molecules were shown to affect leukocyte, endothelial cell, smooth muscle cell and/or thrombocyte function, the likelihood of their role in cardiovascular damage related to renal failure is described. In addition, the middle-molecule behaviour during dialysis is commented. The impact of dialytic removal by diffusion or convection in clinical studies is extensively discussed reflecting the benefit on patient survival and/or clinical outcome. The continuing search for new culprits will result in therapeutic options including improved removal of uremic solutes and/or the search for pharmacological strategies blocking responsible pathophysiological pathways.

Narita, Ichiei; Iguchi, Seitaro; Omori, Kentaro; Gejyo, Fumitake

doi: 10.1093/joneph/21.2.161pmid: N/A

Skin itching (pruritus) affects 50%-90% of patients undergoing peritoneal dialysis or hemodialysis and the symptoms range from localized and mild to generalized and severe. Among the dermatological abnormalities associated with end-stage renal disease, pruritus is the most prevalent. Of all systemic disorders, uremia is the most important cause of pruritus. The mechanism underlying uremic pruritus is poorly understood: secondary hyperparathyroidism, divalent-ion abnormalities, histamine, allergic sensitization, proliferation of skin mast cells, iron-deficiency anemia, neuropathy and neurological changes, or a combination of these have been hypothesized. Severe pruritus not only affects the quality of life but is also associated with poor outcome in chronic hemodialysis patients. No specific, effective treatment is currently available for uremic pruritus. Further studies are necessary to evaluate the long-term efficacy and safety of a novel kappa-opioid agonist, nalfurafine. Early diagnosis and treatment of uremic pruritus focusing on general strategies that include the optimization of dialysis dose, erythropoiesis-stimulating agents, and management of secondary hyperparathyroidism is recommended.

Mandayam, Sreedhar; Shahinian, Vahakn B.

doi: 10.1093/joneph/21.2.166pmid: N/A

This review summarizes the plausible mechanisms of carcinogenesis, critically analyzes the literature on cancer risk and discusses issues of cancer screening in chronic dialysis patients. Despite conflicting results among various studies, there is sufficient evidence to conclude that there is a heightened incidence of at least some cancers in dialysis patients. The data most convincingly support an increased risk of genitourinary malignancies. Screening for the common solid organ cancers (prostate, colon, breast and cervix) should be individualized, and is appropriate only for the minority of patients with a life expectancy on dialysis of 10 years or longer. Further research is needed before routine screening for bladder or renal cell cancers can be recommended.

Cottone, Santina; Lorito, Maria Carmela; Riccobene, Raffaella; Nardi, Emilio; Mulè, Giuseppe; Buscemi, Silvio; Geraci, Calogero; Guarneri, Marco; Arsena, Rosalia; Cerasola, Giovanni

doi: 10.1093/joneph/21.2.175pmid: N/A

Cignarelli, Mauro; Lamacchia, Olga; Paolo, Salvatore Di; Gesualdo, Loreto

doi: 10.1093/joneph/21.2.180pmid: N/A

Type 2 diabetes mellitus is one of the leading causes of end-stage renal disease in the Western world. Smoking can also be seen as a powerful agent, although often underrated, able to induce renal damage and microvascular dysfunction via several different mechanisms, which often overlap with those of diabetic disease, and in concert may eventually worsen the renal redox homeostasis. As a result of this, the association of diabetes with smoking may favor the onset and/or the progression of renal insufficiency toward renal failure, and such a conclusion is supported by an array of epidemiological and physiopathological studies. Consequently, smoking prevention and cessation programs must be strongly encouraged not only to reduce the cardiovascular risk, but also to avoid the deterioration of renal function among diabetic patients.

Cannata-Andía, Jorge B.; Locatelli, Francesco; Zoccali, Carmine

doi: 10.1093/joneph/21.2.190pmid: N/A

Anemia in chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease. Maintenance of stable hemoglobin (Hb) levels is necessary to effectively manage CKD anemia. The European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) endorsed the present CKD Anaemia Physician Behaviours Survey conducted among nephrologists who regularly manage CKD patients. The survey included a total of 369 nephrologists from France, Germany, Italy, Spain and the United Kingdom, between May and June 2007. There were several aspects on which most of the nephrologists (independently of their country of origin) agreed, such as the complexity of managing anemia in patients with comorbidities – particularly, cardiovascular disease and diabetes – the target Hb levels of 11.00 to 12.99 g/dL and the advantages of the flexibility of weekly and monthly dosing. There was also agreement on the fact that most CKD patients are referred to a nephrologist at a late stage of the disease, which makes it difficult to start therapies to reduce morbidity and mortality. The more general implementation of routine glomerular filtration rate estimates in primary care, together with more education and awareness of CKD among primary health care providers, was considered necessary to improve the management of CKD patients.

Bossola, Maurizio; Giungi, Stefania; Panocchia, Nicola; Vulpio, Carlo; Luciani, Giovanna; Tazza, Luigi

doi: 10.1093/joneph/21.2.197pmid: N/A

Background: Being overweight and obesity are associated with improved survival in hemodialysis (HD) patients, based on mechanisms that are presently uncertain. We compared traditional and uremia-related cardiovascular risk factors in HD patients stratified according to their body mass index (BMI).Methods: One hundred sixteen HD patients were stratified into 4 groups according to the BMI: underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9) and obese (≥30). Blood samples were obtained before the HD session to measure serum albumin, high-sensitivity C-reactive protein, fibrinogen, ferritin, total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein A-I and apolipoprotein B-100, apolipoprotein B (apoB) to apolipoprotein A (apoA) ratio and Lp(a) lipoprotein.Results: There were 3 underweight (excluded from the analysis), 58 normal weight, 35 overweight and 20 obese patients. Their mean age was 62.1 ± 14.1 years. There were 68 men and 45 women. Mean dialytic age was 5.32 ± 3.2 years. The mean BMI of the study population was 25.2 ± 4.1. The prevalence of smoking habit was similar in the 3 groups (17.2%, 8.5% and 25%, respectively; p=0.28). The prevalence of hypertension was higher in overweight (77.1%) and obese (65%) patients than in leaner counterparts (53.4%), although the difference was not significant. Conversely, diabetes prevalence was significantly higher in overweight and obese patients (22.8% and 30%, respectively) than in normal weight patients (6.9%; p=0.02). The serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, Lp(a) lipoprotein, apolipoprotein A-I, apolipoprotein B-100, and apoA/apoB ratio were similar in the 3 BMI groups. Triglycerides levels were significantly higher in obese (221.2 ± 132.7 mg/dL) and overweight (230.5 ± 119.3 mg/dL) patients than in those of normal weight (154.6 ± 78.8 mg/dL; p=0.02). Most of the uremia-related cardiovascular risk factors (anemia, hyperparathyroidism, chronic inflammation) were comparable among BMI categories as well as the levels of C-reactive protein, fibrinogen and ferritin.Conclusion: The present study suggests that almost all traditional and uremia-related cardiovascular risk factors do not differ significantly among different categories of BMI in hemodialysis patients.

Vitale, Corrado; Verdecchia, Claudio; Bagnis, Cristiana; Ganzaroli, Marco; Giorcelli, Giovanni; Marangella, Martino

doi: 10.1093/joneph/21.2.205pmid: N/A

Background: Dermatan sulfate (DS) is a natural glycosaminoglycan with a unique mechanism of action on the coagulation system. Unlike unfractionated heparin (UFH), DS selectively inhibits thrombin, does not inhibit factor Xa, is effective on both free and fibrin-bound thrombin and does not interfere with platelets. This study represents the first experience using DS as anticoagulant in patients on continuous renal replacement therapy (CRRT).Methods: A total of 147 patients in our intensive care unit who developed acute renal failure after cardiovascular surgery were on CRRT according to the same protocol: machine, Gambro Prisma; filter, AN69, 0.9 m2; QB, 150 ml/min; QD, 2,000 ml/hour; and QInfusate, 500 ml/hour. In a retrospective cohort of 100 patients, anticoagulation was performed with UFH (UFH-CRRT): initial bolus of 530 ± 363 IU, then i.v. infusion of 598 ± 261 IU/hour. A prospective cohort of 47 patients received DS (DS-CRRT) as a 150-mg bolus followed by a 13.5 ± 3 mg/hour infusion. Hematology tests were performed at baseline and during CRRT; filter lifetime was measured from the start to filter clotting.Results: Median filter lifetime was 58 hours in DS-CRRT vs. 47 hours in UFH-CRRT (p<0.001). No differences emerged in basal hematology and hemostasis tests between groups. During CRRT, DS produced a smaller activated partial thromboplastin time increase than UFH (p<0.01). Platelet count exhibited a comparable small decline in both DS-CRRT and UFH-CRRT (p<0.01). No significant bleeding episodes occurred during DS-CRRT. In-hospital mortality was similar in the 2 cohorts.Conclusions: DS can be suggested as an anticoagulant for CRRT in patients who develop acute renal failure following major cardiovascular surgery.