Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure.

Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

New measurements of energy expenditure and physical activity in chronic kidney disease.

The accurate estimation of total daily energy expenditure (TEE) in chronic kidney patients is essential to allow the provision of nutritional requirements; however, it remains a challenge to collect actual physical activity and resting energy expenditure in maintenance dialysis patients. The direct measurement of TEE by direct calorimetry or doubly labeled water cannot be used easily so that, in clinical practice, TEE is usually estimated from resting energy expenditure and physical activity. Prediction equations may also be used to estimate resting energy expenditure; however, their use has been poorly documented in dialysis patients. Recently, a new system called SenseWear Armband (BodyMedia, Pittsburgh, PA) was developed to assess TEE, but so far no data have been published in chronic kidney disease patients. The aim of this review is to describe new measurements of energy expenditure and physical activity in chronic kidney disease patients.

Genetic loci influencing kidney function and chronic kidney disease.

Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.

Effect of oral calcium carbonate on aortic calcification in apolipoprotein E-deficient (apoE-/-) mice with chronic renal failure.

BACKGROUND: In chronic kidney disease (CKD) patients, the intake of calcium-based phosphate binders is associated with a marked progression of coronary artery and aortic calcification, in contrast to patients receiving calcium-free phosphate binders. The aim of this study was to reexamine the role of calcium carbonate in vascular calcification and to analyse its effect on aortic calcification-related gene expression in chronic renal failure (CRF). METHODS: Mice deficient in apolipoprotein E underwent either sham operation or subtotal nephrectomy to create CRF. They were then randomly assigned to one of the three following groups: a control non-CRF group and a CRF group fed on standard diet, and a CRF group fed on calcium carbonate enriched diet, for a period of 8 weeks. Aortic atherosclerotic plaque and calcification were evaluated using quantitative morphologic image processing. Aortic gene and protein expression was examined using immunohistochemistry and Q-PCR methods. RESULTS: Calcium carbonate supplementation was effective in decreasing serum phosphorus but was associated with a higher serum calcium concentration. Compared with standard diet, calcium carbonate enriched diet unexpectedly induced a significant decrease of both plaque (p<0.05) and non-plaque-associated calcification surface (p<0.05) in CRF mice. It also increased osteopontin (OPN) protein expression in atherosclerotic lesion areas of aortic root. There was also a numerical increase in OPN and osteoprotegerin gene expression in total thoracic aorta but the difference did not reach the level of significance. Finally, calcium carbonate did not change the severity of atherosclerotic lesions. CONCLUSION: In this experimental model of CRF, calcium carbonate supplementation did not accelerate but instead decreased vascular calcification. If our observation can be extrapolated to humans, it appears to question the contention that calcium carbonate supplementation, at least when given in moderate amounts, necessarily enhances vascular calcification. It is also compatible with the hypothesis of a preponderant role of phosphorus over that of calcium in promoting vascular calcification in CRF.

Bolus injections of synthetic atrial natriuretic peptide in patients with chronic renal failure or nephrotic syndrome.

The diuretic and natriuretic responses to exogenous synthetic atrial natriuretic peptide (ANP) were evaluated in patients with chronic renal failure (CRF) or nephrotic syndrome (NS). Patients were studied after an oral water load (8 ml/kg in CRF and 20 ml/kg in NS patients). A short intravenous bolus of either a placebo or ANP was administered when urine output was stable. In each group of patients, three doses of ANP were injected at 24 h intervals, i.e., 1.0, 1.5, and 2.0 micrograms/kg in the CRF and 1.0, 1.5, and 3.0 micrograms/kg in the NS group. Blood pressure and heart rate were monitored throughout the study and urinary volume and electrolyte excretion were measured every 20 min up to 3 h after the bolus. An acute and transient fall in blood pressure was observed immediately after the ANP injection. It was more pronounced in CRF than in NS patients. In CRF patients, ANP caused only a slight increase in urinary volume (13.5-44% over baseline) but a significant increase in urinary sodium excretion (45-114% over baseline). In NS patients, significant increases in both urine volume (60-105%) and sodium excretion (149-248%) were also found. In these latter patients, the renal response to ANP appeared to be better preserved. The hemodynamic and renal changes induced by ANP occurred mainly during the first 20 min following the ANP administration, when the peak plasma ANP levels were obtained. However, no clear dose-response effect could be evidenced in either group with the three doses of ANP chosen in this study.

Psychological profile of adolescents with a kidney transplant.

To describe the psychological profile of renal transplant adolescents compared to healthy peers and to adolescents with CKD, three groups of adolescents aged 12-18 yr were selected: TX, CX, and adolescents with CKD. Psychiatric symptoms and disorders were evaluated through direct interviews (K-SADS-PL) and self-report questionnaires (YSR and CBCL). Forty TX (14 LRD and 26 DD transplant recipients), 40 CX and 20 CKD were included. Twelve of 40 (30%) TX, three of 20 (15%) CKD, and three of 40 (7.5%) CX had a history of learning difficulties (p = 0.03). Compared to CX, TX had lower total YSR competencies score (p = 0.028) and lower total CBCL competencies score (p = 0.003). Twenty-six of 40 (65%) TX, 12 of 20 (60%) CKD and 15 of 40 (37.5%) CX (p = 0.038) met DSM-IV diagnostic criteria for lifetime psychiatric disorder, with rates of depressive disorder of 35% among TX and CKD compared to 15.2% among CX (p = 0.043). Eight of 40 (20%) TX had a history of simple phobia. Nine of 40 (22.5%) TX met diagnostic criteria for ADHD as compared to one of 20 (5%) CKD and three of 40 (7.5%) CX. In the TX group, we found no significant differences in educational and psychiatric variables between LRD and DD. In conclusion, we found a high prevalence of psychiatric morbidity (depression, phobia, ADHD), educational impairment and social competence problems in the TX group. CKD scored in between TX and CX on most measures.

Immunosuppression in hepatitis C virus-infected patients after kidney transplantation.

Hepatitis C virus (HCV) infection is an important health problem in kidney transplant recipients with a significantly higher prevalence than in the general population. Kidney transplantation remains the treatment of choice for most HCV-infected patients with end-stage kidney disease, in spite of lower patient and graft survival as compared to HCV-negative patients. Immunosuppression likely has significant consequences on HCV replication and/or disease after transplantation. However, determining the best immunosuppressive strategies after kidney transplantation in the presence of HCV infection remains challenging. The use of induction therapy is not contraindicated, and a short-course induction may actually be beneficial in HCV-infected kidney transplant recipients. Corticosteroid withdrawal may be an acceptable option in HCV-infected patients with specific comorbidities such as diabetes mellitus or osteoporosis. The best calcineurin inhibitor to be used in HCV-infected patients remains to be determined, as there is a lack of large controlled trials addressing this particular issue. Overall, immunosuppressive regimens need to be individualized according to clinical parameters other than HCV, such as the patient's immunological risk and other comorbidities. In conclusion, there is a need for prospective controlled studies to define the optimal immunosuppressive regimen in HCV-infected kidney transplant recipients.

Genome-wide association and functional follow-up reveals new loci for kidney function.

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

Influence of CD4+/CD25+ regulatory T cells on atherogenesis in patients with end-stage kidney disease.

Atherosclerosis, which is influenced by both traditional and nontraditional cardiovascular risk factors and has been characterized as an inflammatory process, is considered to be the main cause of the elevated cardiovascular risk associated with chronic kidney disease. The inflammatory component of atherosclerosis can be separated into an innate immune response involving monocytes and macrophages that respond to the excessive uptake of lipoproteins and an adaptive immune response that involves antigen-specific T cells. Concurrent with the influx of immune cells to the site of atherosclerotic lesion, the role of the adaptive immune response gradually increases. One of those cells are represented by the CD4+/CD25+ Tregs, which play indispensable roles in the maintenance of natural self-tolerance and negative control of pathological, as well as physiological, immune responses. Altered self-antigens such as oxidized LDLs may induce the development of CD4+/CD25+ Tregs with atheroprotective properties. However, atherosclerosis may be promoted by an imbalance between regulatory and pathogenic immunity that may be represented by the low expression of the forkhead box transcription factor (Foxp3) in CD4+/CD25+ Tregs. Such a defect may break immunologic tolerance and alter both specific and bystander immune suppression, leading to exacerbation of plaque development. Patients with end-stage kidney disease (ESKD) display a cellular immune dysfunction and accelerated atherosclerosis. Uremic solutes that accumulate during ESKD may be involved in these processes. In patients with ESKD and especially in those that are chronically hemodialyzed, oxidative stress induced by oxidized LDLs may increase CD4+/CD25+ Treg sensitivity to Fas-mediated apoptosis as a consequence of specific dysregulation of IL-2 expression. This review will focus on the current state of knowledge regarding the influence of CD4+/CD25+ Tregs on atherogenesis in patients with ESKD, and the potential effect of statins on the circulating number and the functional properties of these cells.

Fibrose rétropéritonéale: cause rare d'insuffisance rénale postrénale, a ne pas méconnaître [Retroperitoneal fibrosis: a rare cause of postrenal kidney failure, no to be missed].

We report the observation of a fifty years old man, admitted in the emergency room for bilateral lumbar pain and hyperkaliemic metabolic acidosis, and postrenal kidney failure induced by bilateral hydronephrosis. Radiographic exploration and histologic studies of biopsy confirmed an idiopathic retroperitoneal fibrosis that clinically and biologicaly responded to three seances of hemodialysis, and insertion in each uretere of one double J stent, and long term corticotherapy. The retroperitoneal fibrosis is a little common inflammatory disease, characterized by the development of a fibrous mass around the retroperitoneal structures. His diagnostic means evolved. On the other hand, his treatment was the object of no checked controlled and randomized trial. This article proposes an updating of the knowledge on this subject.

Urine Fetuin-A is a biomarker of autosomal dominant polycystic kidney disease progression.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by numerous fluid-filled cysts that frequently result in end-stage renal disease. While promising treatment options are in advanced clinical development, early diagnosis and follow-up remain a major challenge. We therefore evaluated the diagnostic value of Fetuin-A as a new biomarker of ADPKD in human urine. RESULTS: We found that renal Fetuin-A levels are upregulated in both Pkd1 and Bicc1 mouse models of ADPKD. Measurement by ELISA revealed that urinary Fetuin-A levels were significantly higher in 66 ADPKD patients (17.5 ± 12.5 μg/mmol creatinine) compared to 17 healthy volunteers (8.5 ± 3.8 μg/mmol creatinine) or 50 control patients with renal diseases of other causes (6.2 ± 2.9 μg/mmol creatinine). Receiver operating characteristics (ROC) analysis of urinary Fetuin-A levels for ADPKD rendered an optimum cut-off value of 12.2 μg/mmol creatinine, corresponding to 94% of sensitivity and 60% of specificity (area under the curve 0.74 ; p = 0.0019). Furthermore, urinary Fetuin-A levels in ADPKD patients correlated with the degree of renal insufficiency and showed a significant increase in patients with preserved renal function followed for two years. CONCLUSIONS: Our findings establish urinary Fetuin-A as a sensitive biomarker of the progression of ADPKD. Further studies are required to examine the pathogenic mechanisms of elevated renal and urinary Fetuin-A in ADPKD.