Intrarenal activation of renin angiotensin system in the development of cyclosporine A induced chronic nephrotoxicity

Background The relationship between cyclosporine-induced chronic nephrotoxicity （CAN） and renin-angiotenein II in humans is still contradictory. This study was conducted to detect the levels of renin and angiotensin II （ANGII） both in renal tissue and plasma from kidney transplantation patients suffering from CAN. Methods Twenty-six patients with allograft biopsy-proven CsA-related chronic nephrotoxicity （CAN group） and chronic rejection （control group） were enrolled in this study. Renal tissues were subjected to immunohistochemical staining with renin and ANGII antibodies. Renin and ANGII plasma levels were measured when the biopsy was performed. The relationship between expression of renin or ANGII and clinicopathological manifestations were also investigated. The cyclosporine plasma level was obtained 2 hours after morning dose （C2）. In vitro, human umbilical vein endothelial cells （HUVEC） and rat mesangial cells （MC） were incubated with different concentrations of CsA （0, 250, 500, 1000 μg/L） for 24 hours. Secretion and expression of renin and ANGII was measured by radioimmunoassay or immunohistochemical staining. Results Renal pathological scores for renin and ANGII expression were significantly higher in specimens of CAN than in controls （P 〈0.05）. The plasma levels of renin, ANGII and C2 in the CAN group were higher than the control group, but no significant difference was found （（0.37±0.12） ng·ml^-1·h^-1 vs （0.20±0.10） ng·ml^-1·h^-1, P=0.076; （122.69±26.73） pg/ml vs （121.88±36.35） pg/ml, P=0.977; （719.04±55.89） ng/ml vs （658.80±90.78） ng/ml, P=0.196, respectively）. In vitro, renin as well as ANGII expression increased significantly in both HUVEC and MC after the cells were incubated with CsA for 24 hours （P 〈0.05）. CsA also stimulated the secretion of ANGII in HUVEC and MC in a dose-dependent manner. Conclusions Renal allograft biopsy is important to differentiate chronic CsA-related nephropathy from chronic rejection. The intrarenal renin angiotensin system plays an important role in CsA-related chronic nephropathy. The histological lesions of CsA nephrotoxicity fail to correspond spontaneously to either the change of C2 level or the change of renin and ANGII plasma level. CsA stimulates the secretion of ANGII and the expression of renin and ANGII in HUVEC and MC. Blockage of RAS may be helpful for therapeutic intervention in the progression of CsA-related chronic nephropathy.

Recurrence of primary hyperoxaluria after kidney transplantation： the report of two cases

Primary hyperoxaluria （PH） is a rare autosoma recessive disorder of glyoxylate metabolism in which specific hepatic enzyme deficiencies result in overproduction of oxalate. Because oxalate is excreted exclusively by the kidney, hyperoxaluria leads to calcium oxalate nephrolithiasis, nephrocalcinosis, and renal failure. PH are considered rare with a prevalence of 0.1-0.2 per 106 population.2 PH was misdiagnosed in some cases initially and unfortunately a case may not be detected until the post-transplant period by allograft biopsy.

Prevalence, awareness, treatment, and control of hypertension in the non-dialysis chronic kidney disease patients

Background Data on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease （CKD） patients are limited.The aim of the present study was to investigate the prevalence,awareness,treatment,and control of hypertension in the non-dialysis CKD patients through a nationwide,multicenter study in China.Methods The survey was performed in 61 tertiary hospitals in 31 provinces,municipalities,and autonomous regions in China （except Hong Kong,Macao,and Taiwan）.Trained physicians collected demographic and clinical data and measured blood pressure （BP） using a standardized protocol.Hypertension was defned as systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg,and/or use of antihypertensive medications.BP 〈140/90 mmHg and 〈130/80 mmHg were used as the 2 thresholds of hypertension control.In multivariate logistic regression with adjustment for sex and age,we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.Results The analysis included 8927 non-dialysis CKD patients.The prevalence,awareness,and treatment of hypertension in non-dialysis CKD patients were 67.3%,85.8%,and 81.0%,respectively.Of hypertensive CKD patients,33.1% and 14.1% had controlled BP to 〈140/90 mmHg and 〈130/80 mmHg,respectively.With successive CKD stages,the prevalence of hypertension in non-dialysis CKD patients increased,but the control of hypertension decreased （P〈0.001）.When the threshold of BP 〈130/80 mmHg was considered,the risk of uncontrolled hypertension in CKD 2,3a,3b,4,and 5 stages increased 1.3,1.4,1.4,2.5,and 4.0 times compared with CKD 1 stage,respectively （P〈0.05）.Using the threshold of 〈140/90 mmHg,the risk of uncontrolled hypertension increased in advanced stages （P〈0.05）.Conclusions The prevalence of hypertension Chinese non-dialysis CKD patients was high,and the hypertension control was suboptimal.With successive CKD stages,the risk of uncontrolled hypertension increased.