Significant increase in plasma 4β-hydroxycholesterol concentration in patients after kidney transplantation

Several previous studies have shown that renal failure decreases not only renal elimination but also metabolic clearance of drugs, particularly those metabolized by CYP3A. However, whether recovery of renal function results in recovery of hepatic CYP3A activity remains unknown. In this study, we evaluated the effect of renal function on CYP3A activity after kidney transplantation in patients with end-stage renal disease (ESRD) by measuring the change in CYP3A activity using plasma concentration of 4β-hydroxycholesterol as a biomarker. The study enrolled 13 patients with ESRD who underwent the first kidney allograft transplantation. Morning blood samples were collected before and 3, 7, 10, 14, 21, 30, 60, 90, 120, 150 and 180 days after kidney transplantation. Plasma concentration of 4β-hydroxycholesterol was measured using GC-MS. Compared with before kidney transplantation, creatinine clearance increased significantly from day 3 after kidney transplantation and stabilized thereafter. Plasma concentration of 4β-hydroxycholesterol was elevated significantly on days 90 and 180 after kidney transplantation. In conclusion, this study suggests the recovery of CYP3A activity with improvement in renal function after kidney transplantation in patients with ESRD.     

Renal function outcomes after nephrectomy for kidney cancer in elderly patients

The kidneys are organs with multiple functions and essential to maintain life. Ablative procedures, such as nephrectomy, diminish nephron mass and can have a potentially negative impact on renal function. We investigated renal function outcome in patients who underwent nephrectomy for renal cell cancer with special emphasize on elderly patients. Data from 104 patients who underwent nephrectomy for kidney cancer in the Department of Urology, University Hospital Rijeka from January 2005 to December 2010 were retrospectively analyzed. All patients had a normal concentration of serum creatinine and a normal contralateral kidney before surgery. Renal function, as estimated by the glomerular filtration rate (eGFR), was determined before and after nephrectomy using the abbreviated Modification of Diet in Renal Disease equation. We compared the eGFR before and after nephrectomy in the patients of different age. The mean preoperative eGFR was 75.2 mL/min, and the mean postoperative eGFR was 52.7 mL/min (p < 0.0001). In the group of patients > or = 65 years old, the mean preoperative GFR was 69.2 mL/min, and the mean postoperative eGFR was 47.4 mL/min (p < 0.0001). Our data indicate that the eGFR significantly decreased after nephrectomy for kidney cancer. In elderly patients, diminished renal function following nephrectomy was more prominent.     

Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: a position statement

The systematic staging of chronic kidney disease (CKD) by glomerular filtration measurement and proteinuria has allowed the development of rational and appropriate management plans. One of the barriers to early detection of CKD is the lack of a precise, reliable and consistent measure of kidney function.The most common measure of kidney function is currently serum creatinine concentration. It varies with age, sex, muscle mass and diet, and interlaboratory variation between measurements is as high as 20%.The reference interval for serum creatinine concentration includes up to 25% of people (particularly thin, elderly women) who have an estimated glomerular filtration rate (eGFR) that is significantly reduced (< 60 mL/min/1.73 m). The recent publication of a validated formula (MDRD) to estimate GFR from age, sex, race and serum creatinine concentration, without any requirement for measures of body mass, allows pathology laboratories to "automatically" generate eGFR from data already acquired. Automatic laboratory reporting of eGFR calculated from serum creatinine measurements would help to identify asymptomatic kidney dysfunction at an earlier stage. eGFR correlates well with complications of CKD and an increased risk of adverse outcomes such as cardiovascular morbidity and mortality. We recommend that pathology laboratories automatically report eGFR each time a serum creatinine test is ordered in adults. As the accuracy of eGFR is suboptimal in patients with normal or near-normal renal function, we recommend that calculated eGFRs above 60 mL/min/1.73 m be reported by laboratories as "> 60 mL/min/1.73 m", rather than as a precise figure.     

Significant decrease in plasma midregional proadrenomedullin level in patients with end-stage renal disease after living kidney transplantation

Impaired renal function has been suggested to significantly impact plasma midregional proADM (MR-proADM) level. The aim of this study was to assess whether improvement of renal function after living kidney transplantation has an impact on plasma MR-proADM-like immunoreactive substance (IS) level. Eleven patients with end-stage renal disease (ESRD) who were scheduled to undergo the first living kidney allograft transplantation were enrolled. Plasma MR-proADM-IS levels were measured before and 3, 7, 10, 14, 21, 30, 60 and 90 days after kidney transplantation. Plasma MR-proADM-IS level decreased significantly from day 3 after kidney transplantation compared to before kidney transplantation. A significant negative correlation was observed between creatinine clearance and plasma MR-proADM-IS level from before to 90 days after kidney transplantation (r_s = −0.70, p < 0.0001). These results suggest that recovery of kidney function after kidney transplantation may lead to decrease in plasma MR-proADM level in patients with ESRD, and that plasma MR-proADM level may depend largely on renal function.     

Serum levels of the adipokine chemerin are increased in preeclampsia during and 6 months after pregnancy

Preeclampsia is a serious cardiovascular complication in pregnancy which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, chemerin was introduced as a novel adipokine inducing insulin resistance in vitro and in vivo. In the current study, we investigated serum concentrations of chemerin by ELISA in control and preeclampsia patients during pregnancy (Control: n=37, preeclampsia: n=37) and 6 months after delivery (Control: n=35, preeclampsia: n=36). Furthermore, the association between chemerin and markers of renal function, glucose and lipid metabolism, as well as inflammation was studied in pregnant patients. Median maternal chemerin concentrations were significantly elevated in preeclampsia patients (249.5 [range: 123.1-366.9] μg/l) as compared to controls (204.8 [138.5-280.8] μg/l) (p<0.001). Furthermore, chemerin serum levels positively correlated with blood pressure, creatinine, free fatty acids, cholesterol, triglycerides (TG), leptin, adiponectin, and C-reactive protein in univariate analyses. In multivariate analyses, TG and leptin remained independently associated with circulating chemerin. Interestingly, median chemerin concentrations 6 months after delivery remained significantly higher in former preeclampsia patients (196.0 [119.8-368.7] μg/l) as compared to controls (152.2 [102.8-216.4] μg/l). Taken together, maternal chemerin serum concentrations are significantly increased in preeclampsia during and after pregnancy. Furthermore, TG and leptin are independent predictors of circulating chemerin during pregnancy.     

Circulating endoglin concentration is not elevated in chronic kidney disease

Background

Soluble endoglin, a TGF-β receptor, plays a key role in cardiovascular physiology. Whether circulating concentrations of soluble endoglin are elevated in CKD or underlie the high risk of cardiovascular death associated with chronic kidney disease (CKD) is unknown.

Methods

Individuals with and without CKD were recruited at a single center. Estimated glomerular filtration rate (eGFR) was estimated using the modified MDRD study equation and the serum creatinine at the time of recruitment, and patients were assigned to specific CKD stage according to usual guidelines. Serum endoglin concentration was measured by ELISA and univariate and multivariable regression was used to analyze the association between eGFR or CKD stage and the concentration of soluble endoglin.

Results

Serum endoglin was measured in 216 patients including 118 with stage 3 or higher CKD and 9 individuals with end stage renal disease (ESRD). Serum endoglin concentration did not vary significantly with CKD stage (increase of 0.16 ng/mL per 1 stage increase in CKD, P = 0.09) or eGFR (decrease -0.06 ng/mL per 10 mL/min/1.73 m² increase in GFR, P = 0.12), and was not higher in individuals with ESRD than in individuals with preserved renal function (4.2±1.1 and 4.3±1.2 ng/mL, respectively). Endoglin concentration was also not significantly associated with urinary albumin excretion.

Conclusions

Renal function is not associated with the circulating concentration of soluble endoglin. Elevations in soluble endoglin concentration are unlikely to contribute to the progression of CKD or the predisposition of individuals with CKD to develop cardiovascular disease.     

肾移植术后患者同型半胱氨酸、肾功能和血脂水平的变化及其相关性分析

目的:分析肾移植术后患者血清的同型半胱氨酸(Hcy)、肾功能和血脂水平的变化和相关性,探讨其在肾移植术后评价肾功能的应用价值。方法:将2013年10月~2016年9月就诊于我院确诊慢性肾衰并进行肾移植手术的300例术后随访患者作为观察组,选择同期健康志愿者100例作为对照组。检测并比较两组Hcy、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平。根据观察组患者Hcy水平的不同将其分成Hcy正常组与Hcy异常组,并对比两组患者的血脂指标水平;测定半胱氨酸蛋白抑制剂C(CysC)的水平并计算肾小球滤过率(eGFR);对观察组血清Hcy与eGFR值、血脂指标水平进行相关性分析,并采用Logistic回归分析分析观察组肾移植术后eGFR下降的影响因素。结果:观察组患者的血清Hcy、TC、TG、HDL-C、LDL-C水平均明显高于对照组(P0.05)。Hcy异常组血清LDL-C水平明显高于Hcy正常组,而HDL-C水平明显低于Hcy正常组(P0.05)。观察组患者血清Hcy与eGFR、HDL-C水平呈负相关关系(r=-0.573、-0.414,P0.05);与TG水平呈正相关(r=0.432,P0.05),与TC、LDL-C无相关(P0.05)。多元Logistic回归分析显示,Hcy、TG、LDL-C水平均与患者eGFR下降有关(P0.05)。结论:在肾移植术后,慢性肾衰患者的TG、LDL-C、Hcy水平均升高,且伴有eGFR水平的降低;肾移植术后肾功能的改变与血清TG、LDL-C、Hcy水平相关;检测肾移植患者血脂指标、Hcy的水平可以评估移植肾功能受损情况。     

Urinary Calprotectin and Posttransplant Renal Allograft Injury

Objective

Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury.

Methods

In a multicenter, prospective-cohort study of 144 incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months.

Results

We observed a significant inverse association of urinary calprotectin concentrations and eGFR 4 weeks after transplantation (Spearman r = −0.33; P<0.001). Compared to the lowest quartile, patients in the highest quartile of urinary calprotectin had an increased risk for an eGFR less than 30 mL/min/1.73 m² four weeks after transplantation (relative risk, 4.3; P<0.001; sensitivity, 0.92; 95% CI, 0.77 to 0.98; specificity, 0.48; 95% CI, 0.31 to 0.66). Higher urinary calprotectin concentrations predicted impaired kidney function 4 weeks after transplantation, as well as 6 months and 12 months after transplantation. When data were analyzed using the urinary calprotectin/creatinine-ratio similar results were obtained. Urinary calprotectin was superior to current use of absolute change of plasma creatinine to predict allograft function 12 months after transplantation. Urinary calprotectin predicted an increased risk both in transplants from living and deceased donors. Multivariate linear regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation.

Conclusions

Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation.     

C-Terminal Fragment of Agrin (CAF): A Novel Marker for Progression of Kidney Disease in Type 2 Diabetics

Background

Diabetes is the leading cause of CKD in the developed world. C-terminal fragment of agrin (CAF) is a novel kidney function and injury biomarker. We investigated whether serum CAF predicts progression of kidney disease in type 2 diabetics.

Methods

Serum CAF levels were measured in 71 elderly patients with diabetic nephropathy using a newly developed commercial ELISA kit (Neurotune®). Estimated glomerular filtration rate (eGFR) and proteinuria in spot urine were assessed at baseline and after 12 months follow up. The presence of end stage renal disease (ESRD) was evaluated after 24 months follow-up. Correlation and logistic regression analyses were carried out to explore the associations of serum CAF levels with GFR, proteinuria, GFR loss and incident ESRD. Renal handling of CAF was tested in neurotrypsin-deficient mice injected with recombinant CAF.

Results

We found a strong association of serum CAF levels with eGFR and a direct association with proteinuria both at baseline (r = 0.698, p<0.001 and r = 0. 287, p = 0.02) as well as after 12 months follow-up (r = 0.677, p<0.001 and r = 0.449, p<0.001), respectively. Furthermore, in multivariate analysis, serum CAF levels predicted eGFR decline at 12 months follow-up after adjusting for known risk factors (eGFR, baseline proteinuria) [OR (95%CI) = 4.2 (1.2–14.5), p = 0.024]. In mice, injected CAF was detected in endocytic vesicles of the proximal tubule.

Conclusion

Serum CAF levels reflect renal function and are highly associated with eGFR and proteinuria at several time points. Serum CAF was able to predict subsequent loss of renal function irrespective of baseline proteinuria in diabetic nephropathy. CAF is likely removed from circulation by glomerular filtration and subsequent endocytosis in the proximal tubule. These findings may open new possibilities for clinical trial design, since serum CAF levels may be used as a selection tool to monitor kidney function in high-risk patients with diabetic nephropathy.     

Circulating TNF Receptors 1 and 2 Are Associated with the Severity of Renal Interstitial Fibrosis in IgA Nephropathy

The current study aimed to examine whether the levels of TNF receptors 1 and 2 (TNFR1 and TNFR2) in serum and urine were associated with other markers of kidney injury and renal histological findings, including TNFR expression, in IgA nephropathy (IgAN). The levels of the parameters of interest were measured by immunoassay in 106 biopsy-proven IgAN patients using samples obtained immediately before renal biopsy and in 34 healthy subjects. Renal histological findings were evaluated using immunohistochemistry. The levels of serum TNFRs were higher in IgAN patients than in healthy subjects. The levels of both TNFRs in serum or urine were strongly correlated with each other (r > 0.9). Serum TNFR levels were positively correlated with the urinary protein to creatinine ratio (UPCR) and four markers of tubular damage of interest (N-acetyl-β-D-glucosaminidase [NAG], β2 microglobulin [β2m], liver-type fatty acid-binding protein [L-FABP], and kidney injury molecule-1 [KIM-1]) and negatively correlated with estimated glomerular filtration rate (eGFR). Patients in the highest tertile of serum TNFR levels showed more severe renal interstitial fibrosis than did those in the lowest or second tertiles. The tubulointerstitial TNFR2-, but not TNFR1-, positive area was significantly correlated with the serum levels of TNFRs and eGFR. Stepwise multiple regression analysis revealed that elevated serum TNFR1 or TNFR2 levels were a significant determinant of renal interstitial fibrosis after adjusting for eGFR, UPCR, and other markers of tubular damage. In conclusion, elevated serum TNFR levels were significantly associated with the severity of renal interstitial fibrosis in IgAN patients. However, the source of TNFRs in serum and urine remains unclear.     

Influence of AHRR Pro189Ala polymorphism on kidney functions

The function of aryl hydrocarbon receptor repressor (AHRR) in the kidney is unclear. The present study investigated associations between AHRR Pro189Ala polymorphism and estimated glomerular filtration rates (eGFR), serum creatinine, and hemoglobin levels in 2775 Japanese adults without diabetes. In addition, we examined whether AHRR expression levels in the kidney of control and chronic kidney disease (CKD) rats were changed. Multiple linear regression analyses showed that carriers of the Ala allele had increased eGFR and lower concentrations of serum creatinine and hemoglobin (p < 0.05). Immunohistochemical analysis showed that the expression of AHRR was upregulated in the kidneys of rats with CKD. These findings suggest that AHRR plays distinct roles in kidney functions and hemoglobin values. The effects of the AHRR polymorphism might be intensified in the kidneys of patients with CKD.     

尿铜蓝蛋白、肾损伤因子1与糖尿病肾病患者肾功能的关系及对预后不良的预测价值研究

摘要 目的：探讨尿铜蓝蛋白（CP）、肾损伤因子1（KIM-1）与糖尿病肾病（DKD）患者肾功能的关系及对预后不良的预测价值。方法：回顾性分析2017年1月～2019年1月陆军第八十二集团军医院肾内科收治的160例DKD患者（DKD组）的临床资料,随访3年,根据是否发展为终末期肾脏疾病（ESRD）分为预后不良组42例和预后良好组118例,另选取同期56例单纯2型糖尿病（T2DM）患者作为T2DM组和47例体检健康者作为对照组。采用微量法和酶联免疫吸附试验法检测尿CP、KIM-1水平,并计算尿白蛋白/肌酐比值（UACR）和估算肾小球滤过率（eGFR）。通过Spearman相关性分析DKD患者尿CP、KIM-1与UACR、eGFR的相关性,单因素和多因素Logistic回归分析DKD患者预后不良的影响因素,受试者工作特征（ROC）曲线分析尿CP、KIM-1对DKD患者预后不良的预测价值。结果：随访3年,160例DKD患者有42例发展为ESRD,预后不良发生率为26.25％（42/160）。DKD组尿CP、KIM-1、UACR高于T2DM组、对照组,eGFR低于T2DM组、对照组（P＜0.05）;T2DM组尿CP、KIM-1、UACR高于对照组,eGFR低于对照组（P＜0.05）。Spearman相关性分析显示,DKD患者尿CP、KIM-1与UACR呈正相关（P均＜0.001）,与eGFR呈负相关（P均＜0.001）。多因素Logistic回归分析显示,高血压、DKD分期4期和糖化血红蛋白（HbA1c）（较高）、低密度脂蛋白胆固醇（LDL-C）（较高）、UACR（较高）、尿CP（较高）、尿KIM-1（较高）为DKD患者预后不良的独立危险因素（P＜0.05）,eGFR（较高）为独立保护因素（P＜0.05）。ROC曲线分析显示,尿CP、KIM-1联合预测DKD患者预后不良的曲线下面积大于各指标单独预测。结论：DKD患者尿CP、KIM-1升高与肾功能降低和预后不良密切相关,尿CP、KIM-1联合预测DKD患者预后不良的价值较高。     

Serious renal transplant rejection and adrenal hypofunction after gradual withdrawal of prednisolone two years after transplantation.

Ten patients with stable renal function two years after transplantation had their sole immunosuppressive treatment (oral prednisolone 10 mg daily) withdrawn by reducing the daily dose by 1 mg at monthly intervals. Plasma prednisolone concentration, cortisol concentration, creatinine clearance, and serum creatinine concentration were measured in all patients, and the adrenal response to corticotrophin was determined in five by measuring plasma cortisol concentrations before and after tetracosactrin injection. No episodes of rejection occurred in patients taking over 7 mg prednisolone daily. Although three patients apparently required only minimal immunosuppressive treatment (less than 5 mg daily) the remainder suffered episodes of rejection at daily doses below 7 mg. There was a tenuous association between rejection and low plasma cortisol concentration, but neither the pattern of plasma prednisolone concentrations nor the response to tetracosactrin were related to episodes of rejection. Reducing the daily dose of oral prednisolone to under 7 mg should not be attempted in patients with renal transplants unless there are extenuating circumstances.     

Ten-Year Follow-up of Patients with Epidemic Post Infectious Glomerulonephritis

BackgroundScarce information on outcomes of epidemic post infectious glomerulonephritis is available. This is a 10-year follow-up of the patients that developed acute glomerulonephritis in an epidemic outbreak caused by group C Streptococcus zooepidemicus in Brazil in 1998, that were also previously evaluated 2 and 5 years after the acute episode.MethodsIn this prospective study 60 cases (out of 134 in 1998) were reevaluated after 10 years, as well as community controls matched by gender and age. They underwent clinical and renal function evaluation, including serum creatinine and cystatin C, estimated glomerular filtration rate (eGFR), albuminuria and hematuria.ResultsComparisons of clinical and renal function aspects of 60 patients and 48 community controls have not shown significant differences (eGFR <60 ml/min/1.73m² and/or albuminuria >30mg/g creatinine: 13.8% vs. 12.2%, respectively, p = 0.817) except for a higher frequency of hypertension in the cases (45.0% vs. 20.8%, p = 0.009). Comparing the same patients affected in the acute episode, 2, 5 and 10 years later, it was observed an improvement of median eGFR levels at 2 years and a trend toward subsequent stabilization in these levels, associated with decrease in albuminuria and increased hypertension rates in the last survey. At 10 years it was not observed additional reduction of renal function using serum creatinine, eGFR and cystatin C.ConclusionsDuring the acute episode of epidemic GN a considerable proportion of patients presented hypertension and reduced renal function; after 2 years and particularly at this 10-year follow-up survey there was no worsening of renal function parameters, except for persistent higher frequency of hypertension. Nevertheless, a longer follow up is necessary to confirm that progressive loss of renal function will not occur.     

慢性肾脏病患者血清GDF-15的水平及临床意义

目的:探讨慢性肾脏病(Chronic Kidney Disease,CKD)患者血清生长分化因子-15(Growth Differentiation Factor-15,GDF-15)的表达及与其他肾功能相关临床指标的相关性。方法:选取西南医科大学附属医院2017年3月至2017年7月健康体检中心30例健康体检者对照组及肾病内科、内分泌科、心内科住院病房各期CKD患者150例,采用ELISA法测试验检其血清GDF-15水平。结果:除去CKD1期外,各期CKD患者eGFR及血清SCr、BUN、GDF-15水平均明显高于健康对照组,差异具有统计学意义(P0.05);随着CKD分期的增加,患者血清SCr、BUN、GDF-15浓度逐渐增加,且各组之间差异具有统计学意义(P0.05)。CKD3组患者血清UA浓度明显高于健康对照组、CKD1组(P0.05),CKD4组、CKD5组血清UA浓度明显高于健康对照组、CKD1组及CKD2组(P0.05)。GDF-15水平与eGFR水平呈负相关(r=-0.768,P0.01),与SCr水平呈正相关(r=0.751,P0.01),与BUN水平呈正相关(r=0.764,P0.01),与UA水平呈正相关(r=0.470,P0.01)。结论:GDF-15与慢性肾脏病的发生与发展密切相关。     

Association of High-Density Lipoprotein Cholesterol with the Estimated Glomerular Filtration Rate in a Community-Based Population

Background

Reduced kidney function is independently associated with low high-density lipoprotein cholesterol (HDL-C) levels in patients with end-stage renal disease (ESRD), those on hemodialysis, and those with stage 3–5 chronic kidney disease (CKD). However, epidemiological data investigating the relationship between HDL-C levels and kidney function in the general population with roughly normal kidney function are limited, and the results are also inconsistent. The aim of this study was to evaluate the relationship between HDL-C levels and the estimated glomerular filtration rate (eGFR) in a community-based population in China.

Methods

This was a community-based cross-sectional survey. In total, 4925 participants (age range, 18–96 years; mean, 51.30±11.98 years) were recruited during routine health status examinations. A questionnaire was used to ascertain age, smoking status, and the history of hypertension and diabetes mellitus for each participant. We measured the body mass index, waist circumference, systolic and diastolic blood pressure, and fasting glucose, total cholesterol, triglyceride, HDL-C, low-density lipoprotein cholesterol, uric acid, and serum creatinine level of each participant. eGFR was evaluated using the Chinese modified Modification of Diet in Renal Disease equation.

Results

The HDL-C level was higher in the first quartile (lowest quartile) of eGFR than in the fourth quartile (the highest quartile). Additionally, HDL-C levels decreased as eGFR decreased. Pearson’s correlation analysis revealed that HDL-C levels were associated with eGFR (r=0.16). After adjustment for some confounders, HDL-C was independently associated with all quartiles of eGFR in the participants.

Conclusions

HDL-C was independently associated with kidney function in a community-dwelling general population. The association between low HDL-C levels and a decreased eGFR gradually strengthened as eGFR declined.     

Plasma ghrelin levels in patients with end-stage renal disease

Ghrelin is an acylated peptide stimulating secretion of the growth hormone (GH). It was originally isolated from the rat stomach as an endogenous ligand for the growth hormone secretagogue receptor. Although being predominantly produced by endocrine cells of the gastric fundus, its secretion has been found in various tissues including the kidney. To study the influence of renal failure on plasma ghrelin levels we examined 16 patients with end-stage renal disease (ESRD) receiving hemodialysis (8 men and 8 women) and 19 controls (10 men and 9 women). Both groups were comparable in age and BMI. In all subjects we assessed plasma levels of ghrelin, leptin, soluble leptin receptor, insulin, IGF-I, IGFBP-1, IGFBP-3 and IGFBP-6. Ghrelin levels were significantly higher in the group of dialyzed patients (4.49+/-0.74 vs. 1.79+/-0.15 ng/ml; p<0.001). These patients had significantly higher levels of GH, IGFBP-1, IGFBP-6, leptin and percentage of body fat (p<0.05). In the group of patients with ESRD plasma ghrelin levels positively correlated with IGFBP-1 (p<0.01). In the control group, ghrelin positively correlated with GH concentrations (p<0.01) and negatively correlated with the levels of insulin and creatinine (p<0.05). In conclusion, patients with ESRD have higher ghrelin concentrations, which might be caused by a decreased excretion/metabolism of ghrelin in the kidney during renal failure.     

Asymmetrical (ADMA) and symmetrical dimethylarginine (SDMA) as potential risk factors for cardiovascular and renal outcome in chronic kidney disease – possible candidates for paradoxical epidemiology?

Summary. Background: Asymmetrical dimethylarginine (ADMA) is an inhibitor of nitric-oxide synthase. It has been linked to atherosclerotic risk in the general population as well as in end-stage renal disease patients (ESRD), whereas symmetrical dimethylarginine (SDMA) is thought to be biological inactive. Prospective data concerning the role of both dimethylarginines are rare in patients with chronic kidney disease. Methods: 200 patients with chronic kidney disease (mean age 57.6 ± 13.0 years, 69 female, 131 male); 82 with chronic renal failure (CRF), 81 on maintenance haemodialysis (HD) and 37 renal transplant recipients (RTR) were prospectively followed for 24 months. ADMA and SDMA were measured by HPLC. The relation of plasma levels of ADMA and SDMA together with conventional risk factors for the cardiovascular and renal outcome was investigated with Cox proportional hazards model. Results: Mean serum levels of SDMA were significantly increased in all groups compared to the control group (P ≤ 0.0005), ADMA was increased only in HD and RTR (P ≤ 0.004). Forty-seven cardiovascular events (CVE) occurred during follow-up, 35 patients died, and 39 patients reached ESRD. Multivariate analysis showed diabetes (RR 3.072, P = 0.01), ESRD (RR 11.915, P < 0.0005), elevated CRP levels (RR 3.916, P < 0.0005) and surprisingly a lower ADMA level (RR 0.271, P = 0.008) as independent risk factors for CVE. Serum creatinine (RR 11.378, P = 0.001), haemoglobin (RR 0.710, P = 0.038 for an increment of 1 mmol/l), and SDMA levels (RR 1.633, P = 0.006, per 1 μmol/l increment) were predictors for the progression to ESRD. Conclusions: Data from a heterogeneous group of patients with chronic kidney disease provide evidence that conventional risk factors seem to play a more important role than elevated serum levels of ADMA or SDMA for cardiovascular events. Increasing serum SDMA concentration seems to play an additive role for the renal outcome besides serum creatinine and haemoglobin levels. Whether ADMA might possibly be a candidate for the phenomenon of “paradoxical epidemiology” in chronic kidney disease needs further investigation.     

Short and Long-Term Effects of Telaprevir on Kidney Function in Patients with Hepatitis C Virus Infection: A Retrospective Cohort Study

Background

Recent reports suggest that telaprevir, a protease inhibitor used to treat hepatitis C infection, is associated with decline in kidney function during therapy, particularly in patients with baseline renal impairment.

Methods

Patients treated with telaprevir in a single healthcare network were retrospectively reviewed. Kidney function was determined at baseline, during therapy, and twelve weeks and twelve months after telaprevir discontinuation. Significant creatinine rise during therapy was defined as an increase in serum creatinine ≥ 0.3mg/dL from baseline during treatment with telaprevir.

Results

Between July 2011 to January 2013,seventy-eight patients began treatment. The majority completed the prescribed twelve weeks of telaprevir therapy; 32% discontinued due to side effects. The average rise in serum creatinine during therapy was 0.22mg/dL (standard deviation 0.22mg/dL). Thirty-one percent experienced a significant creatinine rise during therapy. Decline in estimated glomerular filtration rate (eGFR) was lower in those with baseline eGFR < 90 mL/min/1.73m² compared to the group with baseline eGFR ≥ 90 mL/min/1.73m² (12 vs. 18 mL/min/1.73m², P = 0.047). Serum creatinine fully normalized by twelve weeks after cessation of telaprevir in 83% of patients, however experiencing a significant creatinine rise during telaprevir use was associated with a 6.6mL/min/1.73m² decrease in estimated glomerular filtration rate at twelve months in an adjusted model.

Conclusions

Decline in kidney function during therapy with telaprevir is common and is not associated with baseline eGFR < 90mL/min/1.73m² as previously reported.     

Role of the kidney in regulating plasma immunoreactive beta-melanocyte-stimulating hormone.

An analysis of the factors that influence the increase in plasma immunoreactive beta-melanocyte-stimulating hormone (beta-MSH) concentration in chronic renal failure showed that: (a) the increase correlated with the increase in serum creatinine concentrations; (b) beta-MSH was not cleared from the plasma by haemodialysis; (c) beta-MSH concentrations increased with length of time on dialysis and increased further after bilateral nephrectomy but there was no further increase with time; (d) beta-MSH levels decreased to normal after renal transplantation; and (e) beta-MSH was excreted in urine only when plasma levels rose to well above those of chronic renal failure (in Nelson''s syndrome). These findings suggest that the kidney regulated plasma beta-MSH by a non-excretory mechanism and is the major site of beta-MSH metabolism.