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Zeitschrift für Nephrologie und Therapeutik

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Volumen 2, Ausgabe 1 (2012)

Forschungsartikel

Beneficial Effect of Rhein on the Treatment of Diabetic Nephropathy in Nonobese Diabetic (NOD) Mice

Zhonghui Jia,Xiaohua Guo,Jianping Wang,Zhihong Liu*

Objective: Rhein has been discovered early to have the function of inhibiting both electron transfer and ADP- driven H + uptake in mitochondria. It has been also found that rhein can inhibit the up regulation of GLUT1 (glucose transporting protein-1) function and the activity of hexosamine biosynthetic pathway in mesangial cells in vitro. Futhermore, we have showed the renal protective effect of rhein on STZ-induced diabetic rats. So we try to explore the therapeutic effects of rhein on diabetic nephropathy (DN) in another diabetic model of NOD mice.
Methods: In our study, NOD mice of eight weeks of age were injected intraperitoneally four times with STZ (50 mg/kg) at 7-day interval. Mice with glycosuria and plasma glucose level above 14.0 mmol/L were verified for diabetes. Diabetic NOD mice were subdivided into control and rhein treatment groups. Mice in rhein treatment group were continuously administraed with rhein (150 mg/kg/d) for 15 weeks after diabetes was developed. Plasma parameters (including plasma glucose and lipid level), urinary protein level and histopathology of kidneys were all observed at the end of the experiment.
Results: We demonstrate that rhein not only reduced the urinary protein excretion (0.37 ± 0.17 vs 3.32 ± 0.68 mg/24h, P<0.05), but also prevent the elevation of serum creatinine in diabetic mice after treatment of 15 weeks. In addition, rhein led to a marked decrease of plasma glucose level in experimental model, this effect reached its peak at 15 weeks (7.8 ± 3.80 vs 31.9 ± 4.77 mmol/L, P<0.01), accompanied with decrease of plasma triglyceride (0.74 ± 0.13 vs 2.16 ± 0.73 mmol/L, P<0.01) and cholesterols (1.84 ± 0.55 vs 6.53 ± 5.27 mmol/L, P<0.01). The morphologic studies showed the diabetic NOD mice present glomerular hypertrophy, mesangial expansion and diffuse sclerosis. The accumulation of fibronectin and deposition of immunoglobulin examined by immunostaining in glomeruli were found decreased in rhein-treated NOD mice. Examinition of pancreatic islet sections from NOD mice revealed peri-islet and intraislet mononuclear cells filtration. Treatment with rhein ameliorated cellular aggregation. Stain with Gomori aldehyde fuchsine method showed that loss of β-cells was reduced in rhein-treated mice. Conclusions: Taken together, these results indicate that rhein is able to ameliorate hyperglycemia and halt the progression of diabetic nephropathy in NOD mice, which possesses potential foreground on the management of human diabetes and its complications.

Forschungsartikel

Efficacy of Cinacalcet for the Treatment of Secondary Hyperparathyroidism in CKD Patients on Peritoneal or Hemo Dialysis: The Middle-East Experience

Abdullah Al-Hwiesh*,Ahmed Alsaloom,Krishan Lal Gupta,Ibrahiem Saee,Raja Ramchandran,Fahad Al-Mohanna

Background:Management of secondary hyperparathyroidism is challenging with traditional therapy. The calcimimetic cinacalcet hydrochloride acts on the calcium-sensing receptors to increase its sensitivity to calcium, thereby reducing parathyroid hormone (PTH) secretion. Calcimimetics lower parathyroid hormone levels without increasing calcium and phosphorus levels.

Aim:To evaluate effectiveness of cinacalcet hydrochloride in reducing serum intact PTH levels in patients with end stage renal diseases and secondary hyperparathyroidism.

Material methods: The study included patients who were receiving regular dialysis and had inadequately controlled secondary hyperparathyroidism despite standard treatment (calcium based phosphorus binders and/or sevlamer carbonate at ceiling doses with or without vitamin D sterols - 1,25(OH)2-vitamin D). They were assigned to receive cinacalcet (Group I, n= 69; 45 on hemodialysis and 24 on peritoneal dialysis) or their usual drugs without cinacalcet (Group II, n= 40; 20 on hemodialysis and 20 on peritoneal dialysis) for 12 months. Once-daily doses of cinacalcet hydrochloride was increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of < 300 pg/ml. Serum calcium, phosphorous and iPTH were monitored before starting cinacalcet, at 3 months, 6 months and 12 months.

Results: Overall the mean intact PTH before start of therapy was 1086 ± 84.52 pg/ml (cinacalcet-group I) and 644.9 ± 86.58 pg/ml (no-cinacalcet group II) [p= 0.60]. At the end of the study these levels changed to 465.1± 46.51 pg/ml and 914± 173.6 pg/ ml respectively [p=0.01]. Serum calcium at 12 months was higher in the cinacalcet group compared to controls. Serum phosphorus was higher in the cinacalcet group at the start of therapy and persisted to remain so till end of study at 12 months

Conclusion:Cinacalcet effectively lowers parathyroid hormone levels in patients receiving dialysis and having uncontrolled secondary hyperparathyroidism. Frequent monitoring and adequate replacement with calcium and vitamin D sterols prevent hypocalcemia with cinacalcet therapy. Thus, cinacalcet is a goad therapeutic option for controlling secondary hyperparathyroidism in end-stage renal disease patients on both hemo and peritoneal dialysis.

Sonderartikel

Calciphylaxis: Current Management and Emerging Therapies

Eleftheriadis T ,Leivaditis K ,Antoniadi G ,Vassilios Liakopoulos *

Calciphylaxis or calcific uremic arteriolopathy is a relatively uncommon condition with poor prognosis. Although it is predominantly observed in patients with end stage renal disease, a few cases of patients without kidney failure have been reported. Calciphylaxis is characterized by calcification of the arteriolar intima media and eventually by vascular thrombosis, tissue ischemia and painful skin necrosis. Septicemia is the main cause of death. According to published literature concerning the pathology of calciphylaxis, prevention and treatment are principally based on interventions in calcium and phosphorus metabolism. Although novel therapies have emerged, due to the rarity of this condition, there is no sufficient data in favor of a certain treatment.

Forschungsartikel

Urinary NGAL in Prediction of Acute Kidney Injury

Nilgün Tekkeşin*

The incidence of acute kidney injury (AKI, previously referred to as acute renal failure) is reaching epidemic pro- portions. In this situation, early intervention can significantly improve the prognosis. Despite significant improvements in therapeutics, the mortality and morbidity associated with AKI remain high. A major reason for this is the lack of early markers for AKI, akin to troponins in acute myocardial disease, and hence an unacceptable delay in initiating therapy. Unfortunately, serum creatinine (SCr) is a delayed and unreliable indicator of AKI. The authors have previo - usly shown that urine neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of acute kid- ney injury (AKI) after cardiopulmonary bypass (CPB). In this study, the evidence for the role of NGAL measurements in AKI after CPB is explored. The emerging utility of standardized clinical platforms for reliable measurement of NGAL urine is discussed. In a prospective study with 303 adults undergoing CPB were enrolled and serial urine NGAL me- asurements were obtained. The primary outcome was AKI, defined as a >50% increase in SCr. AKI developed in 75 patients (25%), but the diagnosis using Scr was delayed by 2 to 3 d after CPB. In contrast, mean urine NGAL levels increased 4-fold within 2 h after CPB and remained significantly elevated for the duration of the study. The 2-h posto - perative urine NGAL levels strongly correlated with change in creatinine (r =0.56, p<0.001), duration of AKI (r =0.47, p<0.001), and length of hospital stay ( r =0.39, p<0.001). The 12-h urine NGAL levels stromgly correlated with death (r=0.41, p<0.004). Urine NGAL is an early predictive biomarker of AKI severity and mortality after CPB. It will be impor - tant in future studies to validate the sensitivity and specificity of NGAL concentration measurements in clinical samp - les from large cohorts and from multiple clinical situations. Such studies will be facilitated by the anticipated widesp - read availability of standardized commercial tools in the near future.

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