Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI)

Background and objectives

Novel urinary kidney damage biomarkers detect AKI after cardiac surgery using cardiopulmonary bypass (CPB-AKI). Although there is growing focus on whether AKI leads to CKD, no studies have assessed whether novel urinary biomarkers remain elevated long term after CPB-AKI. We assessed whether there was clinical or biomarker evidence of long-term kidney injury in patients with CPB-AKI.

Design, setting, participants, & measurements

We performed a cross-sectional evaluation for signs of chronic kidney injury using both traditional measures and novel urinary biomarkers in a population of 372 potentially eligible children (119 AKI positive and 253 AKI negative) who underwent surgery using cardiopulmonary bypass for congenital heart disease at Cincinnati Children’s Hospital Medical Center between 2004 and 2007. A total of 51 patients (33 AKI positive and 18 AKI negative) agreed to long-term assessment. We also compared the urinary biomarker levels in these 51 patients with those in healthy controls of similar age.

Results

At long-term follow-up (mean duration±SD, 7±0.98 years), AKI-positive and AKI-negative patients had similarly normal assessments of kidney function by eGFR, proteinuria, and BP measurement. However, AKI-positive patients had higher urine concentrations of IL-18 (48.5 pg/ml versus 20.3 pg/ml [P=0.01] and 20.5 pg/ml [P<0.001]) and liver-type fatty acid–binding protein (L-FABP) (5.9 ng/ml versus 3.9 ng/ml [P=0.001] and 3.2 ng/ml [P<0.001]) than did AKI-negative patients and healthy controls.

Conclusions

Novel urinary biomarkers remain elevated 7 years after an episode of CPB-AKI in children. However, there is no conventional evidence of CKD in these children. These biomarkers may be a more sensitive marker of chronic kidney injury after CPB-AKI. Future studies are needed to understand the clinical relevance of persistent elevations in IL-18, kidney injury molecule-1, and L-FABP in assessments for potential long-term kidney consequences of CPB-AKI.     

Hypercalciuria and kidney function in children with haemophilia

Adults with haemophilia have a higher incidence of chronic kidney disease than general male population. We recently showed that children with haemophilia have higher urinary calcium excretion and lower whole body bone mineral density than controls in spite of prophylaxis with the deficient coagulation factor concentrate, serum vitamin D concentrations comparable to those of healthy children and physically active lifestyle. Persistent hypercalciuria may result in nephrocalcinosis and impact renal function. This study sought to assess persistence of urinary calcium excretion and kidney function in children with haemophilia. We investigated retrospectively urinary calcium excretion in 30 children with haemophilia (mean age 12.5 years) from consecutive urine samples over a 2‐year period. Renal evaluation included blood and urine specimen, blood pressure, and renal ultrasound. High number of children with haemophilia had intermittent hypercalciuria. Hypercalciuria was not associated with age, severity of haemophilia or previous hypercalciuria. Kidney function and renal ultrasound were normal with the exception of suspected kidney stone in one patient with haemophilia and transient hypercalciuria. Vitamin D concentrations improved after the families had received information and recommendations concerning vitamin D substitution. Our findings indicate that haemophilia per se predisposes to hypercalciuria which may in turn affect bone mineral content and kidney function. Whether childhood‐onset intermittent hypercalciuria contributes to hypertension and renal complications in adulthood remains to be elucidated in future studies.     

Atrial natriuretic peptide in liver cirrhosis with mild ascites

To clarify the involvement of atrial natriuretic peptide (ANP) in the pathogenesis of liver cirrhosis, we measured plasma ANP in patients with various stages of cirrhosis and in age-matched normal subjects. Urinary cyclic guanosine monophosphate (cGMP) was also measured as a marker of active biological ANP. In addition, effects of exogenous synthetic human ANP (0.5 micrograms/kg) on renal functions were examined in normal subjects and in cirrhotics without ascites or with mild ascites. Plasma ANP levels were not significantly different among these 3 groups. Urinary cGMP concentrations were significantly higher in both cirrhotics without ascites and cirrhotics with mild ascites, (340 pmol/ml, P less than 0.05 and 496 pmol/ml, P less than 0.01 respectively) than normal subjects (95 pmol/ml). In normal subjects, marked increases in urinary volume (UV), sodium excretion (UNaV), fraction excretion of sodium (FENa) and free water clearance (CH2O) were induced after ANP infusion, and significant recoveries were subsequently observed in these parameters. However, in cirrhotics, the responses to ANP infusion of UV, FENa and CH2O were far less dramatic. The response of UV, UNaV and FENa in cirrhotics with mild ascites was delayed compared to cirrhotics without ascites. These results suggest that the blunted natriuretic responsiveness to ANP is contributory to the pathogenesis of initial sodium retention in cirrhotics.     

Sodium Alginate Oligosaccharides Attenuate Hypertension and Associated Kidney Damage in Dahl Salt-Sensitive Rats Fed a High-Salt Diet

Objectives: In this article, the antihypertensive effects of sodium alginate oligosaccharides, enzymatic products of high molecular natural alginate from sea weeds, in Dahl salt-sensitive (Dahl S) rats were investigated. Material and Methods: Dahl S rats fed a high-salt (4% NaCl) diet were treated with sodium alginate oligosaccharides (4% or 8% w/w) for 7 weeks. Systolic blood pressure (SBP) was measured by the tail-cuff method, and hypertensive cardiovascular benefits and kidney damage were assessed. Glomerular function and morphological sclerosis were determined. Results: SBP increased in an age-dependent manner in the untreated Dahl S rats. Sodium alginate oligosaccharide treatment attenuated the increase in SBP in a dose-dependent manner. The heart and aortic walls weighed less in the rats treated with sodium alginate oligosaccharides than in the untreated rats. The SBP reduction was associated with a decrease in urinary protein excretion and an increase in the creatinine clearance rate. Sodium alginate oligosaccharides significantly attenuated hypertensive glomerular sclerosis and arterial injury in the kidney. Fractional excretion of sodium (FENa) decreased in low-salt Dahl S rats and increased with a salt challenge. The alginate oligosaccharides decreased FENa in high-salt Dahl S rats. Conclusions: The results of this study suggest that sodium alginate oligosaccharides attenuate salt-induced hypertension in Dahl S rats. This reduction is associated with decreases in cardiovascular and renal damage.     

Evaluation of kidney damage in patients with acute lymphoblastic leukemia in long-term follow-up: value of renal scan

In order to evaluate potential long-term kidney damage of childhood leukemia and risk factors affecting renal damage, we studied 116 children treated for acute lymphoblastic leukemia (ALL) using the St. Jude Total XI and XIII protocols in 1991-1998. The median follow-up period after the completion of treatment was 35 months. The following parameters were examined: urinalysis, urinary creatinine (Cr), calcium (Ca), phosphorus, beta2-microglobulin, glomerular filtration rate (GFR), tubular phosphorus reabsorption (TPR), and renal function tests. Radiological evaluation included renal ultrasonography (US), and renal scans with DMSA or MAG-3 were performed. Blood chemistry and renal US patients were normal in all patients except two. GFR, TPR, urinary Ca/Cr, beta2-microglobulin, and renal scan were abnormal in 19.0%, 16.4%, 13.8%, 6.0%, and 40.5% of patients, respectively. The abnormality rate in GFR was significantly higher in patients <2 years of age. TPR abnormality was found to be significantly higher in patients who did not have G-CSF. An abnormal renal scan was associated with Hb < 10 g/dL, kidney infiltration, or hypertension at presentation and also occurred patients who underwent methotrexate treatment with frequent intervals during the follow-up period. Patients should be followed-up after cessation of therapy with the conventional tests mentioned above. In case of any abnormality, further detailed tests should be performed; renal scan seems to be more predictive for renal damage.     

Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure

AIM:To investigate serum cystatin C level as an early biomarker for predicting acute kidney injury(AKI)in patients with acute-on-chronic liver failure(ACLF).METHODS:Fifty-six consecutive patients with hepatitis B virus-related ACLF who had normal serum creatinine(Cr)level(<1.2 mg/dL in men,or<1.1 mg/dL in women)were enrolled in the Liver Failure Treatment and Research Center of Beijing 302 Hospital between August 2011 and October 2012.Thirty patients with chronic hepatitis B(CHB)and 30 healthy controls in the same study period were also included.Measurement of serum cystatin C(CysC)was performed by a particle-enhanced immunonephelometry assay using the BN Prospec nephelometer system.The ACLF patients were followed during their hospitalization period.RESULTS:In the ACLF group,serum level of CysC was 1.1±0.4 mg/L,which was significantly higher(P<0.01)than those in the healthy controls(0.6±0.3mg/L)and CHB patients(0.7±0.2 mg/L).During the hospitalization period,eight ACLF patients developed AKI.Logistic regression analysis indicated that CysC level was an independent risk factor for AKI development(odds ratio=1.8;95%CI:1.4-2.3,P=0.021).The cutoff value of serum CysC for prediction of AKI in ACLF patients was 1.21 mg/L.The baseline CysC-based estimated glomerular filtration rate(eGFR CysC)was significantly lower than the creatinine-based eGFR(eGFR CG and eGFR MDRD)in ACLF patients with AKI,suggesting that baseline eGFR CysC represented early renal function in ACLF patients while the Cr levels were still within the normal ranges.CONCLUSION:Serum CysC provides early prediction of renal dysfunction in ACLF patients with a normal serum Cr level.     

Serum carnitine levels and carnitine esters of patients after kidney transplantation: role of immunosuppression

Serum levels of carnitine and carnitine esters were measured in different groups of patients after cadaveric renal transplantation and compared with those of healthy subjects as well as azotemic and uremic patients. In all groups of patients serum levels of total carnitine (TC), free carnitine (FC), short-chain acylcarnitine (SCC), and long-chain acylcarnitine (LCC) increased with reduction of kidney function. However, cyclosporin- and prednisone-treated transplant patients with impaired kidney function displayed significantly higher TC, FC, and SCC compared with transplant patients under immunosuppression with azathioprine and prednisone. This group of cyclosporin-treated patients showed also significantly elevated serum cholesterol suggesting that carnitine deficiency is not responsible for the observed abnormalities in lipid metabolism after renal transplantation. Urinary excretion of TC, FC, SCC, and LCC decreased with reduction of kidney function without differences between cyclosporin- and azathioprine-treated patients. Single dose L-carnitine administration (10 mg/kg body weight IV) resulted in significantly higher TC, FC, SCC, and LCC values of azotemic patients with and without immunosuppression than in healthy subjects. Acylation of the administered carnitine was comparable in healthy controls and azotemic patients. Increased values of short-chain and long-chain acylcarnitine, therefore, seem to depend on the excretion of the diseased kidney(s). Our data demonstrate abnormalities in carnitine metabolism in patients with impaired kidney function. These alterations are further influenced by immunosuppressive drugs.     

Hepcidin, iron status, and renal function in chronic renal failure, kidney transplantation, and hemodialysis

Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. Hepcidin could also act as an indicator of functional iron deficiency in these patients. Cross-sectional study was performed to assess hepcidin correlations with renal function, iron status, and hsCRP in patients with chronic renal failure on conservative treatment, on hemodialyses, and in kidney transplant recipients. Iron status, complete blood count, creatinine, albumin, lipids were assessed using standard laboratory methods. GFR was estimated using MDRD formula. Hepcidin and high sensitivity CRP were measured using commercially available kits. Ferritin and hepcidin were higher in hemodialyzed patients, kidney transplant recipients, and patients with chronic renal failure over controls. In patients with chronic renal failure, hepcidin correlated significantly with total protein, albumin, creatinine, and eGRF. In kidney transplant recipients, hepcidin correlated significantly in univariate analysis, with total protein, ferritin, time after transplantation, creatinine, eGRF and tended to correlate with cholesterol. In hemodialyzed patients hepcidin, correlated significantly with triglycerides, albumin, creatinine, urea, residual renal function, and hsCRP. In healthy volunteers, hepcidin was related to triglycerides and ferritin. Multiple regression analysis in hemodialyzed patients showed that hepcidin was independently related to creatinine, triglycerides, and residual renal function. Multiple regression analysis in kidney transplant recipients showed that hepcidin was independently related only to GFR and ferritin. Elevated hepcidin in all groups of patients studied may be due to low grade inflammation, frequently encountered in this population and mainly to impaired renal function.     

Bloqueo del sistema renina-angiotensina-aldosterona en pacientes con enfermedad renal diabética avanzada

Background and objectives

Diabetic kidney disease is the leading cause of end-stage chronic kidney disease. The renin-angiotensin-aldosterone system (RAAS) blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up.

Parathyroid Enlargement at Dialysis Initiation in Patients With Chronic Kidney Diseases

The kidney chiefly maintains homeostasis of water, electrolytes, and other solutions. When kidney function is reduced, mineral metabolism is disrupted. Mineral and bone disorder in patients with chronic kidney disease associates with increased cardiovascular risk and mortality; however, management of chronic kidney disease–mineral and bone disorder in predialysis patients remains controversial. This study investigates the association between parathyroid enlargement at dialysis initiation and hyperparathyroidism management in dialysis patients. We enrolled 72 patients at dialysis initiation in this study. Using parathyroid sonography, we categorized patients based on presence (detected group; N = 18) or absence (undetected group; N = 54) of enlarged parathyroid glands and assessed the clinical characteristics and laboratory findings. A literature review of ultrasound evaluations of secondary hyperparathyroidism was conducted. Ultrasonography revealed enlarged parathyroid glands in 18 patients (25%). Serum intact parathyroid hormone levels were high in patients with enlarged parathyroid glands; however, of the 29 patients with intact parathyroid hormone levels <240 pg/mL, four had enlarged parathyroid glands. Eight of the 29 patients with serum phosphorus and calcium levels within the optimal range had enlarged parathyroid glands. Twenty of these 29 patients were followed up at 38 ± 17 months (at least 3 months): enlarged parathyroid glands were detected in 6. During follow‐up, serum intact parathyroid hormone levels were significantly higher in the detected group compared with the undetected. In conclusion, enlarged parathyroid glands are frequently detected at dialysis initiation, potentially predicting the persistence of secondary hyperparathyroidism and the need for strict management.     

Bone mineral density of children and adolescents with congenital hypothyroidism

A cross sectional study was made on 60 patients (9.9 +/- 1.8 yr-old) with congenital hypothyroidism (CH) (group A): 40 girls (23 prepubertal) and 20 boys (18 prepubertal). Control group (group B) was constituted of 28 healthy children (10.4 +/- 2.1 yr-old): 18 girls (8 prepubertal) and 10 boys (9 prepubertal). AIMS: To evaluate bone mineral density (BMD) and content (BMC) and to correlate them with chronological and bone age (BA), sex, sexual maturation, l-T4 dose, TSH, TT4, FT4, and CH etiology. BA, total body BMD, and BMC (DXA) were obtained of both groups. TSH, TT4, and FT4 were measured in patients only. BMD was lower in group A (0.795 +/- 0.075 g/cm(2) vs. 0.832 +/- 0.092; p = 0.04) and higher in pubertal than in prepubertal girls (p = 0.004). There was no significant difference between BMD and BMC related to sex and CH etiology. Our data demonstrated that BMD was significantly lower in children with CH, different from what has been published in the literature.     

The role of insulin on renal sodium handling and sympathetic nerve activity in overweight normotensive subjects]

Recently, it was suggested that the role of hyperinsulinemia on the hypertensive mechanism of essential hypertension might be related to renal sodium handling and sympathetic nerve activity, especially in obese hypertensive patients. However, the interrelationship between insulin, obesity, renal sodium metabolism and sympathetic nerve activity in normotensive subjects (NT) still remains unclear. The present study, therefore, was undertaken to clarify the role of insulin on renal sodium handling and sympatho-adrenal function in overweight NT. The study consisted of 24NT, who were divided into two groups of twelve non-obese (NNT) and twelve obese (ONT) subjects. NNT was categorized as a body mass index (BMI) less than, and ONT as a BMI equal to or more than 25kg/m2. In the early morning, after overnight fasting, all subjects remained in a supine state and were examined for renal clearance test. During the two-hour clearance period, mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance(CCr), urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), plasma immunoreactive insulin (IRI), plasma norepinephrine concentration (pNE), and plasma epinephrine concentration (pE) were determined. Although no significant difference was found in age, MAP, HR, pE, CCr or UNaV between the two groups, a significantly higher IRI (p less than 0.05) and lower FENa (p less than 0.05) were observed in ONT than in NNT. There was no significant correlation between IRI and UNaV, FENa or pE in ONT or in NNT. In addition, no significant correlation was shown between FENa and pNE or pE in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum VEGF-D level is correlated with renal dysfunction and proteinuria in patients with diabetic chronic kidney disease

Biomarkers associated with chronic kidney disease (CKD) may play a crucial role in the early diagnosis of diabetic kidney disease. However, there have been few reports published on serum vascular endothelial cell growth factor (VEGF)-D in patients with diabetic CKD. We divided patients with diabetic CKD into two groups: CKD 3–4 and CKD 5. In total, 42 patients with diabetic kidney disease and seven healthy controls without diabetes mellitus were enrolled in this study. An observational study was conducted to evaluate the serum VEGF-D levels and other clinical parameters in each group and to assess the relationship among these factors. The serum levels of VEGF-D were higher in the CKD 3–4 group and CKD 5 group than in the control group. However, there was no significant difference in serum levels of VEGF-D between CKD stage 3–4 group and CKD stage 5 group. Correlation analysis showed that serum VEGF-D was negatively correlated with estimated glomerular filtration rate but positively correlated with serum creatinine, urine albumin-to-creatinine ratio, and urine protein-to-creatinine ratio. Serum VEGF-D was a good biomarker in receiver operating characteristic analysis and independently associated with CKD stages in multiple linear regression analysis. Circulating VEGF-D was positively correlated with blood growth/differentiation factor-15, endostatin, and chemokine (C-X-C motif) ligand 16 levels. Serum VEGF-D levels were correlated with renal dysfunction, albuminuria, and proteinuria in patients with diabetic kidney disease. Elucidation of the role of VEGF-D as a biomarker requires further study.     

Chronic Alcoholism Impedes the Recovery of Renal Function following Renal Ischemia

The recovery of renal function following renal ischemia was studied using rats fed for 1-, 3-, and 5-week periods with an alcoholic diet (ethanol provided 36% of total calories). Renal ischemia was produced by clamping the renal artery and vein for 20 min. Renal function was determined 24 hr after the ischemia. In the absence of ischemic insult, the renal function of rats fed with an alcoholic diet for 1, 3, and 5 weeks was not significantly different from those of nonalcoholic rats. In nonalcoholic rats, renal function (24 hr postischemia) were: glomerular filtration rate (GFR) 430.4 +/- 29.6 microliters/min/g KW (kidney weight), renal plasma flow rate (RPFR) 1.4 +/- 0.17 ml/min/g KW, and fractional sodium excretion (FENa) 2.0 +/- 0.04% (mean +/- SE). Postischemic renal function of rats on 1- and 3-week alcoholic diets were essentially the same as that of the control rats. However, the 24-hr postischemic renal function of 5-week alcoholic diet rats was significantly depressed. The values were only 117.2 +/- 35.2 microliters/min/g KW (p less than 0.05) for GFR, 0.31 +/- 0.12 ml/min/g KW (p less than 0.05) for RPFR, and 7.46 +/- 3.59% for FENa. The present results demonstrate that the rat kidney subjected to prolonged alcohol ingestion was more susceptible to renal insult than a nonalcoholic kidney.     

脓毒症休克合并急性肾损伤早期诊断研究

目的 探讨脓毒症休克合并急性肾损伤( AKI)的早期诊断方法,评价中性粒细胞明胶酶相关脂质运载蛋白(NGAL),白介素18(IL-18)和肾损伤分子1(KIM-1)在脓毒症休克合并AKI早期诊断中的意义. 方法 建立盲肠结扎穿孔(CLP)联合静脉注射内毒素诱导脓毒症休克合并AKI动物模型.将实验用新西兰大白兔70只随机分为对照组(n=35)和造模组(n=35).2组分别于造模后0、3、6、9、12h留取血、尿及组织标本.检测各组兔肾功能指标血肌酐(SCr)和血尿素氮(BUN);取兔肾组织进行病理组织学观察;ELISA法检测各组兔血液NGAL和尿液IL18、KIM-1的含量.结果 与对照组比较,造模组各时间点病理组织学观察均出现不同程度病变.与对照组比较,造模组12h时间点SCr水平明显升高(P＜0.05);BUN各时间点比较无统计学差异(P＞0.05);3h时间点NGAL即明显升高(P＜0.05);KIM-1和IL-18于9h时间点开始明显升高(P均＜0.05). 结论 脓毒症休克合并AKI时肾脏功能受损严重;NGAL和KIM-1可用于脓毒症休克合并AKI的早期诊断和预测.     

Evaluation of combined left ventricular function using the myocardial performance index in children with chronic kidney disease

Background: Myocardial dysfunction that complicates the initial stages of chronic kidney disease (CKD) has not been yet fully characterized in young patients. We aimed to assess the clinical usefulness of myocardial performance index obtained by pulsed‐wave Doppler method (PWD‐MPI) in predicting early disturbances of global left ventricular (LV) function in children with CKD stages 2–4. In addition, we evaluated the clinical utility of tissue Doppler imaging (TDI) as a tool for calculating MPI in comparison with the conventional method. Methods: Standard echocardiography was performed in 34 patients aged 3–18 years and for 35 age‐matched healthy control subjects. PWD‐MPI was calculated from Doppler spectra of mitral inflow and LV outflow. To obtain TDI‐MPI, time intervals were measured from mitral annulus. Results: The mean values of both PWD‐MPI and TDI‐MPI of the patients were significantly different from those of the control subjects. Using receiver operating characteristics curve analysis, TDI‐MPI yielded a better predictive discrimination for separating patients with versus those without myocardial dysfunction than PWD‐MPI. Using a PWD‐MPI >0.36 as the cutoff value, myocardial dysfunction was found with a sensitivity of 64.7% and specificity of 97%. The sensitivity and specificity of TDI‐MPI >0.34 in identification of LV dysfunction were 91% and 82%, respectively. TDI‐MPI was correlated with that measured by PWD (P < 0.004, r = 0.57). Conclusions: Subtle abnormalities of LV function develop early when renal insufficiency is mild to moderate. MPI, measuring by PWD and TDI, are appropriate indicators of overall LV function in young patients with CKD. (Echocardiography 2011;28:97‐103)     

Quality of life in chronic kidney disease

Background — Quality of life (QOL) is suboptimal in end‐stage renal disease. However, studies indicate that QOL is already impaired prior to the initiation of renal replacement therapy, implying that the initial decline originates in the chronic kidney disease (CKD) phase of the renal disease trajectory. Given the significance of QOL as a clinical outcome, there is a paucity of QOL research in CKD. Aims — To measure QOL at three distinct phases (based on creatinine clearance — Ccr) of the disease trajectory in CKD: normal renal function (NRF) with underlying renal disease, moderate CKD, and advanced CKD (Ccr ≥75, 40–60, and ≤30 ml/minute, respectively), and to establish if QOL is different between these groups. Methods — Data was collected from 25 patients from each of the Ccr bands (N=75). We measured self‐reported QOL (Schedule for the Evaluation of Individual Quality of Life — SEIQOL), uraemic symptoms (Leicester Uraemic Symptom Scale — LUSS), and laboratory variables. Results — SEIQOL was significantly lower (p<0.001), and symptom number, frequency, and intrusiveness significantly higher (all p<0.001) in the advanced CKD group when compared to the NRF group. Although SEIQOL and symptom intrusiveness did not differ between the advanced and moderate CKD groups, SEIQOL was significantly lower (p<0.05) and symptom intrusiveness significantly higher (p<0.05) in the moderate CKD group when compared to the NRF group. Conclusion — QOL is already impaired in moderate CKD. The significant difference in QOL and symptom intrusiveness between the moderate CKD and NRF groups may denote a causal relationship between symptom intrusiveness and QOL early in CKD.     

Manejo renal del potasio en la enfermedad renal crónica avanzada: diferencias entre pacientes con o sin hipercaliemia

IntroductionHyperkalemia (HK) is a common electrolyte disorder in chronic kidney disease (CKD), mainly in the advanced stages. A positive potassium balance due to reduced renal excretory capacity is likely the main pathogenic mechanism of HK. Research into the relative role of each pathogenic element in the development of HK in CKD may help to implement more suitable therapies.ObjectiveTo investigate renal potassium handling in advanced CKD patients, and to determine the differences between patients with or without HK.Material and methodsCross-sectional observational study in adult patients with stage 4-5 CKD pre-dialysis. Selection criteria included clinically stable patients and the ability to collect a 24 hour urine sample correctly. Blood and urinary biochemical parameters were analysed including sodium and potassium (K). Fractional excretion of K (FEK) and K load relative to glomerular filtration (Ku/GFR) were calculated. HK was defined as a serum K concentration ≥ 5.5 mmol/l.ResultsThe study group consisted of 212 patients (mean age 65 ± 14 years, 92 females) with a mean GFR of 15.0 ± 4.2 ml/min/1.73 m². 63 patients (30%) had HK. Patients with HK had lower mean bicarbonate levels with respect to patients with normal K levels (NK) (20.3 ± 3.1 vs. 22.8 ± 3.2 mEq/l, P < .0001), but no differences were noted in total urinary sodium and K excretion. While mean FEK values were lower in patients with HK (32.1 ± 12.1% vs. 36.4 ± 14.3%, P = .038), Ku/GFR values were significantly greater with respect to the NK subgroup (4.2 ± 1.5 vs. 3.7 ± 1.4 mmol/ml/min, P = 0,049). FEK showed a strong linear correlation with Ku/GFR (R² = 0.74), and partial linear regressions demonstrated that at a similar Ku/GFR level, the FEK of patients with HK was lower than that of NK patients. By multivariate linear and logistic regression analyses, both FEK and Ku/GFR were shown to be the main determinants of K serum levels and HK.ConclusionsAlthough the K load relative to glomerular filtration (Ku/GFR) is an important determinant of HK in advanced CKD, the most noteworthy characteristic associated with HK in these patients was the limitation of compensatory urinary K excretion, as indicated by lower FEK.     

Urinary vanin‐1 associated with chronic kidney disease in hypertensive patients: A pilot study

Hypertension and chronic kidney disease (CKD) are serious interrelated public health problems. Despite the monitoring and control of high blood pressure, symptoms of CKD are not usually apparent in its early stages. Previously, we reported the utility of urinary vanin‐1 as an early biomarker of kidney injury in spontaneously hypertensive rats, but it remains unknown whether urinary vanin‐1 is associated with CKD in humans. In this study, we estimated associations between urinary vanin‐1 and parameters of kidney function in a cross‐sectional study of hypertensive patients. We measured concentrations of vanin‐1 using spot urine from 147 adult hypertensive patients (mean age, 72.8 years; 39.5% women). Patients were divided into 2 groups based on the median of the estimated glomerular filtration rate (eGFR). The group with eGFR < 60 mL/min per 1.73 m² showed significantly higher levels of urinary vanin‐1 than those with eGFR ≥ 60 mL/min per 1.73 m². On univariate analysis, urinary vanin‐1 as well as neutrophil gelatinase‐associated lipocalin (NGAL) showed significant negative correlations with eGFR; however, multivariate analysis revealed that urinary vanin‐1, but not NGAL, significantly correlated with eGFR. In addition, urinary vanin‐1 had a significant positive correlation with the urinary protein‐to‐creatinine ratio (UPCR) (r = 0.21; P = .021) and albumin‐to‐creatinine ratio (UACR) (r = 0.61; P < .01). In conclusion, urinary vanin‐1 is associated with lower eGFR and higher UPCR and UACR, and might be a potential marker of decreased kidney function in hypertensive patients. Further studies are needed to confirm these findings.     

The Role of Initial Clinical and Laboratory Findingsin Infants With Hyperthyrotropinemia to PredictTransient or Permanent Hypothyroidism

Objective: Studies on the clinical course of children with hyperthyrotropinemia are scarce. We aimed to evaluate the role of presentation findings in such infants to predict eventual outcome.Methods: Files of infants diagnosed as suspicious congenital hypothyroidism (CH) in the neonatal or early infancy period in the past ten years were analyzed retrospectively, and 37 patients (M/F: 20/17) with hyperthyrotropinemia diagnosed at a median age of 3.2 months were included in the study. Criteria for inclusion were: normal free thyroxine (fT4) levels and thyrotropin (TSH) levels between 10-20 μIU/mL during the initial neonatal screening (or TSH<10μIU/mL afterwards). Cases with permanent CH (Group 1) were compared to those with transient hyperthyrotropinemia (Group 2) regarding age at the time of diagnosis, sex, gestational age, birth weight, symptoms, ultrasonographic and scintigraphic findings, initial thyroid function tests, and state of mental and motor development.Results: Of the total group, 20 patients (54%) were eventually diagnosed as permanent CH. T4 doses that maintained normal thyroid function tests were significantly higher at the end of the first and second years of life in this group. Age, TSH and fT4 levels at the time of diagnosis, sex, gestational age, birth weight, symptoms, ultrasonographic and scintigraphic findings, and the state of mental and motor development were similar in the two groups.Conclusions: T4 dose required to maintain a euthyroid state was the only parameter which distinguished between transient and permanent CH.Conflict of interest:None declared.