Is kidney size a useful predictor of renal function in the elderly?

Despite its widespread use, the diagnostic yield of ultrasonography to detect early stages of reduced renal function in the elderly remains doubtful. METHOD: Sixty-two patients (age: 74.8 +/- 6.7 years, 30 females) attending a geriatric ward were examined. Non-insulin-dependent diabetes was present in 28 patients and 32 were hypertensive. Exclusion criteria were previously known renal failure, an elevated serum creatinine above 2 mg/dl at admission or apparent cognitive impairment. Inulin clearance (C(IN)), Cockcroft estimation and urinary albumin excretion rate (UAER) were determined. Renal parenchymal volume, renal volume and mean renal length were calculated using data obtained by ultrasonography. RESULTS: A multiple regression analysis identified C(IN) as the main determining factor on renal parenchymal volume (beta = 0.360; p = 0.004). Body height showed additional influence (beta = 0.295; p = 0.018), but age, gender, diabetes, UAER and hypertension did not. Cockcroft estimation, ultrasonographic markers of renal size and further confounding variables were evaluated in a subsequent multiple regression analysis. Cockcroft estimation explained the major part of the variance (beta = 0.783; p < 0.001) and the occurrence of diabetes showed a borderline additional effect. But there was no supplementary influence of any ultrasonographic parameter. In 11 patients, C(IN) was reduced to < or = 60 ml/min. ROC analysis revealed poor diagnostic efficacy of all ultrasonographic parameters (AUC < 0.7336) compared to Cockcroft estimation (AUC = 0.8718). CONCLUSION: Although a linear relation between C(IN) and renal parenchymal volume could be shown, ultrasonography cannot replace or complement Cockcroft estimation in order to detect early reduced renal function in the elderly. Nevertheless, reduced renal parenchymal volume may occur prior to elevation of serum creatinine in the elderly and should be noted carefully on routine ultrasonographic examinations.     

Asymmetric dimethylarginine: a new player in the pathogenesis of renal disease?

PURPOSE OF REVIEW: This review summarizes current knowledge on asymmetric dimethylarginine, renal function in health and disease, and renal disease progression and examines interventions that may modify the plasma concentration of this methylarginine. RECENT FINDINGS: Nitric oxide deficiency may occur in patients with chronic kidney disease and may contribute to accelerate progression of chronic kidney disease, hypertension and cardiovascular complications. An increase of endogenous nitric oxide inhibitors like asymmetric dimethylarginine seems to play a major role in this process. The kidneys are crucial in both, in re-absorbing and generating L-arginine as well as in eliminating asymmetric dimethylarginine primarily by the enzyme dimethylarginine dimethylaminohydrolase and to a minor degree by urinary excretion. Asymmetric dimethylarginine accumulation predicts both accelerated renal function loss and death in patients with chronic kidney disease and incident cardiovascular complications in patients with end stage renal disease. SUMMARY: Asymmetric dimethylarginine is a new risk factor potentially implicated in the progression of renal insufficiency and in the high rate of cardiovascular complications of patients with chronic kidney disease.     

Asymmetric dimethylarginine: a cardiovascular risk factor in renal disease?

Endothelial dysfunction due to reduced availability of nitric oxide (NO) is an early step in the course of atherosclerotic vascular disease. NO is synthesized from the amino acid L-arginine by the action of the NO synthase (NOS), which can be blocked by endogenous inhibitors such as asymmetric dimethylarginine (ADMA). In laboratory animals, administration of ADMA significantly reduces NO generation, and causes an increase of blood pressure and renal vascular resistance. In clinical studies, a strong correlation between increased ADMA blood levels and impaired endothelial-dependent vasodilatation, and cardiovascular morbidity and mortality has been documented in different populations, including in patients with renal disease. Thus, ADMA seems to be the culprit, and not just an innocent biochemical bystander, of the atherosclerotic disease process. Moreover, reduced NO availability is involved in the progression of renal disease, and increased ADMA blood levels may contribute to this process. Interventions that lower ADMA blood levels in renal patients could, therefore, modulate their atherogenic profile and interfere with progression of renal failure.     

Determination of pyruvate kinase type tumor M2 in human renal cell carcinoma: a suitable tumor marker?

Renal cell carcinoma (RCC) expresses an isoform of the glycolytic enzyme pyruvate kinase (type M2). The dimeric form (TuM2-PK) is over expressed in tumor cells and is detectable in blood with a sensitive enzyme-linked immunosorbent assay (ELISA). The aim of the present study was to evaluate the clinical value of TuM2-PK as a tumor marker for RCC. The TuM2-PK concentration in EDTA-plasma was determined quantitatively and immunologically using an ELISA. We measured the TuM2-PK plasma levels of 83 patients before and after surgery. Ninety-seven patients with various non-malignant diseases were also recruited as a control group. The control group displayed mean levels of 11.37 U/ml of TuM2-PK. Values were elevated in patients with RCC prior to surgery (mean 21.88 U/ml). The plasma levels increased after surgery until day 5 (mean 53.97 U/ml). At day 10, marker levels started to decrease without reaching preoperative values (mean 43.5 U/ml). Plasma levels in the renal vein (obtained during surgery) were not different from those in the peripheral blood. Follow-ups after 2-6 months showed a decrease to below preoperative levels (mean 16.3 U/ml). A significant difference was obtained by comparing the patients according to their Robson score. We found a significant difference (P < 0.01, Wilcoxon's two-sample test) in TuM2-PK levels between patients with RCC and the control group. Nevertheless, using the manufacturer's recommended cut-off value (15 U/ml), sensitivity was only 50.6% and specificity was 80.4%. Our results suggest that TuM2-PK is not a suitable tumor marker for RCC.     

Is Cystatin C a promising marker of renal function, at birth, in neonates prenatally diagnosed with congenital kidney anomalies?

Background Despite the increased prenatal diagnosis of congenital abnormalities of the kidney and urinary tract (CAKUT), no reliable renal marker for glomerular filtration rate (GFR) has been validated yet in neonates. Cystatin C (CysC) is specific to the neonate and is proposed as a sensitive marker for this population. The aims of the study were first to define a reference interval in our center of CysC at birth in normal term babies and assess CysC as a marker of GFR in a group of term neonates prenatally diagnosed with CAKUT compared to controls. Methods One hundred normal term neonates (control group) and 33 neonates with kidney malformation (KM) had the CysC levels in their cord blood measured. A reference interval for CysC in controls was calculated using non-parametric methods. CysC from controls was compared first to the whole group of neonates with KM, then with KM group divided in infants (n = 20) with unilateral kidney malformation (UKM) and those (n = 13) with bilateral kidney malformation (BKM). A multivariable analysis was performed to assess the difference in CysC between the groups with adjustment on other factors. The ability of CysC to discriminate neonates with BKM from the controls was assessed by a non-parametric receiver-operated characteristics (ROC) curve. Results In the control group, the CysC reference interval was [1.54-2.64] mg/L with a median (M) CysC of 2.02 IQR [1.86-2.23]. In the neonates with KM, M CysC was 1.98 IQR [1.79-2.34]; 1.88 IQR [1.76-2.01] in the UKM group and 2.52 IQR [2.16-2.71] in BKM group. Using a multivariate regression analyses, CysC was significantly increased (P < 0.001) in BKM compared to controls with an increment of CysC of 24.5%, and independent from gender, weight and size. The ROC curve analyses, comparing BKM versus controls with a chosen cut-off for CysC of 2.34, showed a sensitivity of 69% and a specificity of 86%. Conclusions Comparing CysC with a reference interval of CysC validated in our center, we showed a significant increase of CysC in neonates presenting BKM compared to controls and those with UKM.     

Does delaying pyeloplasty affect renal function in children with a prenatal diagnosis of pelvi-ureteric junction obstruction?

OBJECTIVE: To evaluate retrospectively children with an antenatal diagnosis of pelvi-ureteric junction (PUJ) obstruction who required pyeloplasty for deteriorating renal function during the follow-up, specifically assessing the recovery of function after surgery. PATIENTS AND METHODS: Between 1988 and 2000, 44 consecutive patients with a prenatal diagnosis of PUJ obstruction who were initially treated by observation underwent pyeloplasty because their renal function deteriorated during the follow-up. Patients with bilateral disease, a single kidney or vesico-ureteric reflux were excluded from the study. The mean (sd) age of the patients was 13.3 (4.5) months and their mean (range) initial renal function 39.7 (30.4-45)%. In all patients the diagnostic criteria and indications for surgery were identical. The main indication for surgery was deteriorating renal function of >5%, confirmed by renal scintigraphy. Of 44 patients, 35 (77%) had severe dilatation of the renal pelvis by >3 cm. The mean (sd) deterioration in renal function during the follow-up, just before surgery, was 8.2 (2.4)%, and the mean time between the last acceptable renogram and the study showing deterioration was 8.3 (1.3) months; the mean follow-up was 5.1 (1.6) years. The results were assessed statistically using the unpaired nonparametric Mann-Whitney U-test. RESULTS: An improvement in hydronephrosis was confirmed in all patients, with renal function returning to the initial levels in 36 of 44 (81%) patients 6-12 months after surgery, although in two patients renal function did not improve after surgery. There was no significant difference between the preoperative characteristics and the degree of hydronephrosis, renal function or patient age with the level of renal functional improvement after surgery. CONCLUSION: In patients with an antenatal diagnosis of PUJ obstruction, expectant management is recommended and spares the children unnecessary surgery. Even if renal function deteriorates, delayed pyeloplasty recovers the initial functional level.     

Is adiponectin a marker of preclinical atherosclerosis in kidney transplantation?

Cañas L, Bayés B, Granada ML, Ibernon M, Porrini E, Benítez R, Díaz JM, Lauzurica R, Moreso F, Torres A, Lampreabe I, Serra A, Romero R. Is adiponectin a marker of preclinical atherosclerosis in kidney transplantation?
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01490.x.
© 2011 John Wiley & Sons A/S. Abstract: The aim of this study was to analyze the relationship between pre‐transplant adiponectin (pre‐ADP), abnormalities in glucose homeostasis (AGH) at three months post‐transplantation, and preclinical atherosclerosis in non‐diabetic patients prior to kidney transplantation (KT). Methods: We carried out a multicenter study in 157 non‐diabetic KT patients (66.5% men; age: 50 ± 13 yr). Pre‐ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima‐media thickness (c‐IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria. Results: Of the patients, 52.8% had AGH. Median pre‐ADP was 19.5 (14–27) μg/mL. An inverse correlation was found between ADP and HOMA index (r = ?0.432; p < 0.001). Median c‐IMT was 0.6 (0.48–0.71) mm. Significant inverse correlation existed between ADP and c‐IMT on both sides (p < 0.05). Patients with c‐IMT >0.6 mm had more AGH (p = 0.012) and lower ADP levels (p = 0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c‐IMT ≥0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c‐IMT. Age, pre‐ADP, and AGH were independent risk factors for elevated c‐IMT. Conclusions: Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis.     

Polythelia: still a marker of urinary tract anomalies in children?

OBJECTIVE: Supernumerary nipples (SNN), or polythelia, are the most common form of the accessory mammary tissue malformation. The frequency of this condition ranges from 0.2% to 5.6% depending on various factors. This condition is associated with several anomalies, although this association is often controversial. The aim of this study was to evaluate the association between SNN and kidney/urinary tract (K/UT) anomalies, where anomalies is taken to mean functional disorders, malformations and diseases. MATERIAL AND METHODS: A case-control study was performed. The study evaluated 166 children (case group) referred to the Pediatric Nephrology Unit of the Department of Pediatrics of the Catholic University of Rome and 182 children (control group) admitted to the Department of Pediatrics because of pathologies not involving the urinary tract. RESULTS: There were 11 children with SNN in the case group, and only two patients in the control group (6.62% vs 1.09%, p<0.05). CONCLUSION: The results show a high incidence of K/UT anomalies in children with SNN, and therefore K/UT should be investigated in this specific population.     

Residual renal function and volume status in peritoneal dialysis patients: a conflict of interest?

Fluid status and volume homeostasis are extremely important in patients with CKD stage 5, as cardiovascular disease, including congestive heart failure and hypertension, is one of the leading causes of death in this patient group. Many epidemiologic studies have meanwhile indicated that indeed preservation of volume control is a key component of adequate peritoneal dialysis. On the other hand, residual renal function is also an important and powerful predictor of outcome in peritoneal dialysis (PD) patients. This has led some authors to advocate a state of "slight fluid overload" to preserve residual renal function. This paper seeks to highlight the idea that probably the reason residual renal function is so important, is that it is elementary in the maintenance of a good fluid balance, and that that reasoning should not be inverted. In addition, we will indicate that volume overload in itself might lead to a faster decline of residual renal function. The paper will also point out some important practice points to avoid deterioration of residual renal function in PD patients, such as strict sodium diet and good glycemic control, that are also key to maintaining a good fluid balance.     

Is the appendix graft suitable for routine biliary surgery in children?

BACKGROUND/PURPOSE: The appendix graft (AG) is used widely for urinary tract replacement in children. Biliary tract replacement is less common. The purpose of this retrospective multicentric study was to evaluate the safety of appendix grafting for biliary reconstruction. METHODS: The files of 33 patients treated at 7 European pediatric centers were reviewed. Indications included choledochal cyst (CC) in 5 cases, biliary trauma (BT) in 1, and biliary atresia (BA) in 27. In CC and BT patients, the graft was inserted isoperistaltically between the proximal biliary duct and second duodenum. In all but one of the BA patients, the graft was placed antiperistaltically by patching its cecal end onto the porta hepatis. RESULTS: Postoperatively, all CC and BT patients initially became asymptomatic but developed laboratory evidence of anicteric cholestasis within 1 year. The most common manifestation was increased gamma-glutamyl-transpeptidase level (GGT), whereas histologic findings showed liver damage (mainly fibrosis). Reoperation has been carried out in 4 CC and 1 BT patients within a mean period of 19 months after appendix grafting. The graft procedure was converted to hepaticojejunostomy (HJ) in 4 and to choledocoduodenostomy in 1. Surgical exploration showed kinking in 1 patient and stenosis in 1. In the remaining 3 cases, there was no discernible cause of cholestasis, and appendix histology findings were normal. In all 5 reoperated patients, liver function findings returned to normal within 1 month. Reoperation is scheduled for the remaining CC patient who currently requires ursodesoxycholic medication to maintain normal liver function and presents histologic evidence of "de novo" sclerosing cholangitis. Results of appendix grafting also were poor in the 27 BA patients. Procedure-related perioperative complications occurred in 4 (15%) including 1 early death from graft necrosis. Another early death resulted from intestinal hemorrhage. Jaundice cleared in only 8 (28%). CONCLUSIONS: The findings of this study suggest that the AG is unsuitable for routine biliary repair in children. It should be used only as a salvage technique when conventional HJ repair is contraindicated. Because of the high risk of graft dysfunction, we recommend screening tests to detect biochemical or histologic cholestasis in any patient previously treated with appendix grafting.     

Is low pre-transplant parathyroid hormone a risk marker for cardiovascular disease in long-term follow-up of renal transplant recipients?

Background

Secondary hyperparathyroidism and altered levels of parathyroid hormone (PTH) are associated with vascular events in chronic kidney disease. After renal transplantation, this association is not clear. Pre-transplant parathyroidectomy (PTX) is common, but post-transplant data are scarce. We aimed to study the effect of PTH at the time of transplantation on risk of post-transplant vascular events in renal transplant recipients with and without pre-transplant PTX.

Methods

258 patients from two Swedish transplant units were followed for 6 years. Separate analyses were made for patients with or without pre-transplant PTX. Patients with no pre-transplant PTX were stratified by quartiles of PTH at time of transplantation and patients with pre-transplant PTX were stratified by above and below median levels of PTH at time of transplantation. Hazard ratios for vascular events, mortality, and graft failure were calculated in adjusted Cox regression models.

Results

In patients with no pre-transplant PTX, the lowest quartile of PTH at transplantation had a higher risk of cardiovascular events compared to quartile 3 with an adjusted hazard ratio (95% CI) of 2.63 (1.04–6.67). In patients with pre-transplant PTX, the group below median of PTH had a higher risk of cardiovascular events with an adjusted hazard ratio (95% CI) of 18.15 (1.62–203.82) compared to patients above median of PTH.

Conclusion

Low levels of parathyroid hormone before transplantation were associated with increased risk of post-transplant vascular events both in patients with and without pre-transplant parathyroidectomy. Any conclusions on causal or direct effect of PTH on outcome cannot be drawn from this observational study.

     

Enhanced plasma levels of advanced glycation end products (AGE) and pro-inflammatory cytokines in children/adolescents with chronic renal insufficiency and after renal replacement therapy by dialysis and transplantation--are they inter-related?

AIMS: Advanced glycation end products (AGEs) are formed by non-enzymatic glycation or glycoxidation. After their interaction with specific receptors, they may induce expression of various proinflammatory cytokines. AGEs were shown to accumulate with advanced age, in diabetes mellitus and, in particular, in patients with chronic renal failure. In contrast to numerous investigations in adults, there are no data on plasma levels of AGEs in children with chronic renal insufficiency (CRI) and after renal replacement therapy. To elucidate the specific role of renal impairment for the formation of AGEs, these data become especially interesting by exclusion of the age-dependent modulatory effects occurring in adults. Therefore, we investigated the concentrations of fluorescent (FL) AGEs, carboxymethyllysine (CML) and markers of inflammation (CRP, IL-6, TNF-alpha) in children/adolescents with chronic renal insufficiency (CRI) and on renal replacement therapy with maintenance dialysis (D) or renal transplantation (TX). PATIENTS: Eleven CRI patients on conservative treatment (CRI, age: mean 12.6, median 12.80, SD 5.8 +/- 1.7 years, serum creatinine: 205.7, 157.5, 58.0 micromol/l, respectively), 10 patients on D (13.6, 13.0, 5.4 years, and 698.2, 633.8, 296.1 micromol/l, respectively) and 9 patients after TX (15.9, 16.0, 3.4 years, and 115.9, 128.0, 35.1 micromol/l, respectively) were included. METHODS: Plasma levels of CML, TNF-alpha, and IL-6 were determined by ELISA, FL-AGEs spectrofluorimetrically (lambda(ex)/lambda(em): 370/440 nm). RESULTS: FL-AGEs and CML levels were increased in all 3 groups with the highest levels in the D patients, a successful renal transplantation did not lead to normalization of plasma AGEs. The mean CRP and IL-6 concentrations were marginally elevated, and no significance among groups was revealed. TNF-alpha was noticeably elevated in all groups, with the highest values in CRI and TX patients, while in the dialysis patients the rise was less pronounced. Stepwise multiple regression did not reveal any correlation between AGEs and proinflammatory parameters, even after exclusion of the TX group from analysis. CONCLUSIONS: In children with CRI and on maintenance dialysis therapy, plasma AGE levels are markedly increased. After renal transplantation, AGE levels decrease without normalization. Proinflammatory parameters (except for TNF-alpha) are only mildly to moderately elevated. No association between AGE levels and data characterizing a proinflammatory state was revealed.