• case report
• chronic kidney disease
• colon rupture
• gastrointestinal bleeding
• gastrointestinal lesion
• sevelamer carbonate

Hyperphosphataemia is an independent risk factor for accelerated cardiovascular disease in chronic kidney disease (CKD), although the mechanism for this is poorly understood. We investigated the effects of sustained exposure to a high-phosphate environment on endothelial function in cellular and preclinical models, as well as in human subjects.

Resistance vessels from rats and humans (± CKD) were incubated in a normal (1.18 mM) or high (2.5 mM) phosphate concentration solution and cells were cultured in normal- (0.5 mM) or high-phosphate (3 mM) concentration media. A single-blind crossover study was performed in healthy volunteers, receiving phosphate supplements or a phosphate binder (lanthanum), and endothelial function measured was by flow-mediated dilatation.

Endothelium-dependent vasodilatation was impaired when resistance vessels were exposed to high phosphate; this could be reversed in the presence of a phosphodiesterase-5-inhibitor. Vessels from patients with CKD relaxed normally when incubated in normal-phosphate conditions, suggesting that the detrimental effects of phosphate may be reversible. Exposure to high-phosphate disrupted the whole nitric oxide pathway with reduced nitric oxide and cyclic guanosine monophosphate production and total and phospho endothelial nitric oxide synthase expression. In humans, endothelial function was reduced by chronic phosphate loading independent of serum phosphate, but was associated with higher urinary phosphate excretion and serum fibroblast growth factor 23.

These directly detrimental effects of phosphate, independent of other factors in the uraemic environment, may explain the increased cardiovascular risk associated with phosphate in CKD.

• cardiovascular risk
• chronic kidney disease
• endothelial function
• nitric oxide
• phosphate

Sevelamer is a phosphate binder widely used in chronic kidney disease (CKD) patients. Sevelamer, as well as other resin-based binders, can crystallize leading to the formation of concretions. Sevelamer crystals (SC) have been associated with gastrointestinal (GI) mucosal injury. We describe three new cases of GI lesions associated with SC and review previously reported cases.

We describe three new cases of GI lesions associated with SC and review previously reported cases.

We found 16 previously reported cases of SC-induced GI lesions. The mean patient age was 61 years (interquartile range 51.5–71.75), 62.5% were females and 10 patients were diabetic. In 13 cases, SC was found inside the GI mucosa. Six patients had history of major abdominal surgery. GI bleeding was the most common clinical symptom (n = 7), with three patients presenting with acute abdomen requiring surgical intervention. Although, SC-induced lesions were observed in all GI segments, intestine was involved in 81% of the cases. Endoscopic examination revealed mainly erosions and ulcerations (n = 7) and pseudoinflammatory polyps (n = 5). No association between sevelamer doses and the severity of GI lesions was found. However, diabetics patients seemed to develop GI lesions with smaller doses of sevelamer as compared with non-diabetic patients, in spite of their fewer GI comorbidities.

SC-induced GI lesions should be considered in CKD patients treated with sevelamer who present GI symptoms, especially lower GI bleeding, once other causes have been ruled out. Diabetics seem more prone to develop SC- associated GI lesions. Sevelamer therapy should be avoided if possible in patients with a history of major abdominal surgery or chronic constipation, because of the high risk of serious GI complications.

• chronic kidney disease
• crystals
• gastrointestinal lesions
• hyperphosphataemia
• sevelamer

• Calcific uremic arteriolopathy
• Calcification
• Chronic kidney disease
• Fibroblast growth factor 23
• Kidney transplantation
• Klotho
• Phosphate binders
• Sevelamer
• Uremia

Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression.

• Chronic kidney disease
• Progression
• Klotho
• Amyloidosis
• Diabetic nephropathy
• Micro RNA

• COX
• MMF
• NSAID
• cyclooxygenase
• mycophenolate mofetil
• nonsteroidal anti-inflammatory drug

• Adrenal Cortex Hormones/adverse effects
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Antibodies, Monoclonal/adverse effects
• Antineoplastic Agents/adverse effects
• Cathartics/adverse effects
• Colchicine/adverse effects
• Contraceptives, Oral/adverse effects
• Diuretics/adverse effects
• Ergotamine/adverse effects
• Esophagitis/chemically induced
• Esophagitis/pathology
• Humans
• Imidazoles/adverse effects
• Intestinal Diseases/chemically induced
• Intestinal Diseases/pathology
• Ion Exchange Resins/adverse effects
• Iron/adverse effects
• Laxatives/adverse effects
• Mycophenolic Acid/adverse effects
• Mycophenolic Acid/analogs & derivatives
• Olmesartan Medoxomil
• Stomach Diseases/chemically induced
• Stomach Diseases/pathology
• Tetrazoles/adverse effects

Prevention and correction of hyperphosphatemia is a major goal of chronic kidney disease–mineral and bone disorder (CKD–MBD) management, achievable through avoidance of a positive phosphate balance. To this aim, optimal dialysis removal, careful use of phosphate binders, and dietary phosphate control are needed to optimize the control of phosphate balance in well-nourished patients on a standard three-times-a-week hemodialysis schedule. Using a mixed diffusive–convective hemodialysis tecniques, and increasing the number and/or the duration of dialysis tecniques are all measures able to enhance phosphorus (P) mass removal through dialysis. However, dialytic removal does not equal the high P intake linked to the high dietary protein requirement of dialysis patients; hence, the use of intestinal P binders is mandatory to reduce P net intestinal absorption. Unfortunately, even a large dose of P binders is able to bind approximately 200–300 mg of P on a daily basis, so it is evident that their efficacy is limited in the case of an uncontrolled dietary P load. Hence, limitation of dietary P intake is needed to reach the goal of neutral phosphate balance in dialysis, coupled to an adequate protein intake. To this aim, patients should be informed and educated to avoid foods that are naturally rich in phosphate and also processed food with P-containing preservatives. In addition, patients should preferentially choose food with a low P-to-protein ratio. For example, patients could choose egg white or protein from a vegetable source. Finally, boiling should be the preferred cooking procedure, because it induces food demineralization, including phosphate loss. The integrated approach outlined in this article should be actively adapted as a therapeutic alliance by clinicians, dieticians, and patients for an effective control of phosphate balance in dialysis patients.

• dialysis
• diet
• food preservatives
• hyperphosphatemia
• phosphate binders
• phosphorus

• calcium
• chronic kidney disease
• phosphate
• mineral and bone disorder
• vascular calcification

• Humans
• Minerals/metabolism
• Parathyroid Glands/physiology
• Renal Dialysis
• Renal Insufficiency, Chronic/blood
• Renal Insufficiency, Chronic/metabolism
• Renal Insufficiency, Chronic/mortality
• Vitamin D/administration & dosage
• Vitamin D/metabolism
• Vitamin D/pharmacology