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Current guidelines recommend under 2g/day sodium intake in chronic kidney disease, but there are a few studies relating sodium intake to long-term outcomes. Here we evaluated the association of mean baseline 24-h urinary sodium excretion with kidney failure and a composite outcome of kidney failure or all-cause mortality using Cox regression in 840 participants enrolled in the Modification of Diet in Renal Disease Study. Mean 24-h urinary sodium excretion was 3.46g/day. Kidney failure developed in 617 participants, and the composite outcome was reached in 723. In the primary analyses, there was no association between 24-h urine sodium and kidney failure (HR 0.99 (95% CI 0.91–1.08)) nor on the composite outcome (HR 1.01 (95% CI 0.93–1.09)), each per 1g/day higher urine sodium. In exploratory analyses, there was a significant interaction of baseline proteinuria and sodium excretion with kidney failure. Using a two-slope model, when urine sodium was under 3g/day, higher urine sodium was associated with increased risk of kidney failure in those with baseline proteinuria under 1g/day and with lower risk of kidney failure in those with baseline proteinuria of ⩾1g/day. There was no association between urine sodium and kidney failure when urine sodium was⩾3g/day. Results were consistent using first baseline and time-dependent urinary sodium excretion. Thus, we noted no association of urine sodium with kidney failure. Results of the exploratory analyses need to be verified in additional studies and the mechanism explored.

Neutrophil gelatinase-associated lipocalin (Ngal, 24p3, SIP24, lipocalin 2, or siderocalin) was originally purified from neutrophils, but with unknown function. Recently, it was identified that Ngal activates nephron formation in the embryonic kidney, is rapidly and massively induced in renal failure and possesses kidney-protective activity. We would like to propose that blood, urine, and kidney Ngal levels are the real-time indicators of active kidney damage, rather than one of many markers of functional nephron number (as Forest Fire Theory). Ngal is a novel iron-carrier protein exerting pleiotropic actions including the upregulation of epithelial marker E-cadherin expression, opening an exciting field in cell biology.

In chronic nephropathies, inhibition of angiotensin-converting enzyme (ACE) is renoprotective, but can further renoprotection be achieved by reduction of blood pressure to lower than usual targets? We aimed to assess the effect of intensified versus conventional blood-pressure control on progression to end-stage renal disease. We undertook a multicentre, randomised controlled trial of patients with non-diabetic proteinuric nephropathies receiving background treatment with the ACE inhibitor ramipril (2·5–5 mg/day). We randomly assigned participants either conventional (diastolic <90 mm Hg; n=169) or intensified (systolic/diastolic <130/80 mm Hg; n=169) blood-pressure control. To achieve the intensified blood-pressure level, patients received add-on therapy with the dihydropyridine calcium-channel blocker felodipine (5–10 mg/day). The primary outcome measure was time to end-stage renal disease over 36 months' follow-up, and analysis was by intention to treat. Of 338 patients who were randomised, three (two assigned intensified and one allocated conventional blood-pressure control) never took study drugs and they were excluded. Over a median follow-up of 19 months (IQR 12–35), 38/167 (23%) patients assigned to intensified blood-pressure control and 34/168 (20%) allocated conventional control progressed to end-stage renal disease (hazard ratio 1·00 [95% CI 0·61–1·64]; p=0·99). In patients with non-diabetic proteinuric nephropathies receiving background ACE-inhibitor therapy, no additional benefit from further blood-pressure reduction by felodipine could be shown.

Purpose: To report a randomized clinical trial designed to determine if remote ischemic preconditioning (IP) has the ability to reduce renal and cardiac damage following endovascular aneurysm repair (EVAR). Methods: Forty patients (all men; mean age 76±7 years) with abdominal aortic aneurysms averaging 6.3±0.8 cm in diameter were enrolled in the trial from November 2006 to January 2008. Eighteen patients (mean age 74 years, range 72–81) were randomized to preconditioning and completed the full remote IP protocol; there were no withdrawals. Twenty-two patients (mean age 76 years, range 66–80) were assigned to the control group. Remote IP was induced using sequential lower limb ischemia. Serum and urinary markers of renal and cardiac injury were compared between the groups. Results: Urinary retinol binding protein (RBP) levels increased 10-fold from a median of 235 µmol/L to 2356 µmol/L at 24 hours (p=0.0001). There was a lower increase in the preconditioned group, from 167 µmol/L to 413 µmol/L at 24 hours (p=0.04). The median urinary albumin:creatinine ratio was significantly lower in the preconditioned group at 24 hours (5 versus 8.8, p=0.06). There were no differences in the rates of renal impairment or major adverse cardiac events. Conclusion: Remote preconditioning reduces urinary biomarkers of renal injury in patients undergoing elective EVAR. This small pilot trial was unable to detect an effect on clinical endpoints; further trials are warranted.

The PROteKT study tested the hypothesis that rosuvastatin can inhibit aminoglycoside-induced nephrotoxicity in children with Cystic Fibrosis (CF). This open label, parallel group, randomised controlled trial recruited children and young people aged 6 to 18 years with CF at 13 paediatric CF treatment centres in the UK. Participants were randomised equally to either receive oral rosuvastatin (10 mg once daily) or no intervention (control) throughout clinically indicated treatment with intravenous tobramycin. The primary outcome was the difference between the groups in mean fold-change in urinary Kidney Injury Molecule-1 (KIM-1). Fifty (rosuvastatin n = 23, control n = 27) participants were recruited between May 2015 and January 2017. Primary outcome data was available for 88% (rosuvastatin n = 20, control n = 24). The estimated mean treatment difference in the geometric mean-fold change of normalised KIM-1 was 1.08 (95% CI 0.87–1.35, p = 0.48). In total there were 12 adverse reactions, all mild, reported by five participants randomised to rosuvastatin, and one serious adverse event in each group. Whilst no protective effect of rosuvastatin was seen, there was a lower than expected level of nephrotoxicity in the cohort. Therefore, we can neither confirm nor refute the hypothesis that rosuvastatin protects against aminoglycoside nephrotoxicity.

Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. Angiotensin-converting enzyme (ACE) inhibitors reduce urine protein excretion and slow the progression of renal disease. The beneficial effect in slowing the progression of renal disease is greater in patients with higher urine protein excretion at the onset of treatment. We hypothesized that the greater beneficial effect of ACE inhibitors on the progression of renal disease in patients with higher baseline levels of proteinuria is due to their greater antiproteinuric effect in these patients. Data were analyzed from 1860 patients enrolled in 11 randomized controlled trials comparing the effect of antihypertensive regimens, including ACE inhibitors to regimens not including ACE inhibitors on the progression of non-diabetic renal disease. Multivariable linear regression analysis was used to assess the relationship between the level of proteinuria at baseline and changes in urine protein excretion during follow-up. The Cox proportional hazards analysis was used to assess the relationship between changes in urine protein excretion during follow-up and the effect of ACE inhibitors on the time to doubling of baseline serum creatinine values or onset of end-stage renal disease. Mean (median) baseline urine protein excretion was 1.8 (0.94) g/day. Patients with higher baseline urine protein excretion values had a greater reduction in proteinuria during the follow-up in association with treatment with ACE inhibitors and in association with lowering systolic and diastolic blood pressures (interaction P < 0.001 for all). A higher level of urine protein excretion during follow-up (baseline minus change) was associated with a greater risk of progression [relative risk 5.56 (3.87 to 7.98) for each 1.0 g/day higher protein excretion]. After controlling for the current level of urine protein excretion, the beneficial effect of ACE inhibitors remained significant [relative risk for ACE inhibitors vs. control was 0.66 (0.52 to 0.83)], but there was no significant interaction between the beneficial effect of ACE inhibitors and the baseline level of urine protein excretion. The antiproteinuric effects of ACE inhibitors and lowering blood pressure are greater in patients with a higher baseline urine protein excretion. The greater beneficial effect of ACE inhibitors on renal disease progression in patients with higher baseline proteinuria can be explained by their greater antiproteinuric effects in these patients. The current level of urine protein excretion is a modifiable risk factor for the progression of non-diabetic renal disease. ACE inhibitors provide greater beneficial effect at all levels of current urine protein excretion.

Background/Aims: There is disagreement regarding the performance of conventional optical microscopy to assess the origin of hematuria. The aim of this study was to determine the optimal cutoff point for dysmorphic cells in order to detect glomerular hematuria by optical and phase-contrast microscopy. Methods: In total, 131 urine samples (66 from patients with glomerulopathies and 65 from nephrolithiasis patients) were evaluated in a blinded fashion. The percentages of doughnut cells and acanthocytes were verified by optical and phase-contrast microscopy. A total of 131 patients were randomly allocated to the derivation (n = 73) and validation (n = 58) groups. Receiver-operating characteristic (ROC) curves were plotted to check the discriminatory power of each group and the best cutoff points were determined by the Youden index in the derivation group and subsequently tested in the validation group. Results: All areas under the ROC curve (AUCs) were statistically significant using both methods (conventional optical and phase-contrast microscopy) and both groups (derivation and validation). AUCs did not differ between different glomerulopathies. The best cutoff point to determine the glomerular origin of hematuria by total dysmorphic cells was 22% using an optical conventional microscope and 40% by phase-contrast microscopy. Conclusion: We determined the best cutoff points to interpret erythrocyte dysmorphism and demonstrated that it is possible to discriminate the origin of hematuria by evaluating erythrocyte dysmorphism in urinalysis using either an optical or a phase-contrast microscope. © 2014 S. Karger AG, Basel

The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease. It is not known whether angiotensin-converting-enzyme (ACE) inhibitors slow the progression of polycystic kidney disease (PKD). We performed a patient-level meta-analysis to compare the effect of antihypertensive regimens, including ACE inhibitors, to those without ACE inhibitors (controls) on kidney disease progression in patients with PKD. We analyzed a database of 11 randomized controlled trials including 1860 patients with nondiabetic kidney disease. We compared randomized groups for the decline in urine protein excretion and kidney disease progression (combined outcome of doubling of baseline serum creatinine or onset of kidney failure). We also performed multivariable linear regression and Cox proportional hazards analyses. Based on previous findings, we searched for interactions between the treatment effect (effect of ACE inhibitors vs. controls) and baseline urine protein excretion in both models. Eight studies included a total of 142 subjects with PKD: 68 (48%) were randomized to ACE inhibitors and 74 (52%) were randomized to the control. Baseline mean (SD) urine protein excretion was 0.92 (1.40) g/day: 1.08 (1.50) g/day in the ACE inhibitor and 0.76 (1.28) g/day in the control group. During a mean follow-up of 2.3 years, mean (SD) urine protein excretion declined by 0.33 (1.11) g/day in the ACE inhibitor group and increased by 0.19 (0.88) g/day in the control group (P < 0.001). Kidney disease progression occurred in 50 patients: 20 patients (29%) in the ACE inhibitor group and 30 patients (41%) in the control group (P = 0.17). ACE inhibitors had a greater effect on lowering urine protein excretion and slowing kidney disease progression in patients with higher levels of baseline urine protein excretion (interaction P < 0.001 and P = 0.03, respectively). As in other causes of non-diabetic kidney disease, antihypertensive regimens with ACE inhibitors are more effective in lowering urine protein excretion in patients with advanced PKD compared to regimens without ACE inhibitors, and this benefit is greater in patients with higher levels of baseline urine protein excretion. The effect of ACE inhibitors to slow kidney disease progression in PKD is inconclusive.

The aim of the study was to find out if there is an optimal mean arterial blood pressure (MABP) during cardiopulmonary bypass (CPB) for renal function in elderly patients during the early postoperative period. We analysed the data of 122 patients >70 years of age with normal preoperative renal function who had been subjected to coronary artery bypass grafting (CABG) procedures on CPB. Patients were divided into 3 groups, according to MABP during CPB: group MP (n=50) included patients whose MABP was maintained between 60–70 mmHg; group LP (n=36), the MABP was <60 mmHg; and group HP (n=36) where the MABP was >70 mmHg. The patients’ clinical data were evaluated during the first three postoperative days. The rate of renal impairment (urine output <50ml/h) in the early postoperative period after cardiac surgery did not differ among the groups. Oliguria developed in 3 patients (6%) of the MP group, in 2 patients (5.6%) in the LP group and in 6 patients (16.7%) in the HP group (χ2=3.6, df=2, p=0.161). Evaluation of MABP on renal excretion showed that there was no difference in urine output among the groups. Serum creatinine levels at the end of the first postoperative day in groups MP, LP and HP were 102.7±20.1, 116.4±58.6 and 113.2±39.8 µmol/L, respectively (F=0.5, df=2, p=0.640). There were no significant differences among the groups at the end of the second and the third day either. Volume balance at the end of surgery and during the early postoperative period was similar in all groups. The need for diuretics did not differ among the groups. The length of postoperative hospital stay was not significantly different among the groups. Our study did not reveal any relationship between a MABP of 48-80 and postoperative renal dysfunction in elderly patients after CABG surgery.

Contrast-induced nephropathy is the third most common cause of acute renal failure in hospitalized patients. The purpose of this study was to compare three supportive treatments for prevention of contrast-induced nephropathy in high-risk patients undergoing coronary angiography. In this randomized clinical trial study, 150 patients with at least one risk factor, such as, congestive heart failure, history of diabetes mellitus, age > 65 years or renal failure were randomly assigned to three equal groups: First group (Sodium (Na) bicarbonate infusion), second group [(N-Acetylcysteine (NAC) + Sodium Chloride (Nacl)], third group (Nacl). Angiography was performed with 350 mgI/mL of Iohexol (Omnipaque). Serum creatinine (Cr), blood blood urea nitrogen (BUN), and urine pH were measured at the start of angiography and 48 hours later. The three groups had no significant difference in demographic characteristics or other risk factors before intervention (P > 0.05). Forty eight hours after exposure, the Cr level increased significantly in the Nacl group (P = 0.039), while these changes were not significant in the other groups (P > 0.05). The incidence of contrast-induced nephropathy was not statistically significant between all the groups (P = 0.944). Although the Cr clearance had no statistically significant difference, it was lower in the NaCl group. Therefore, Na bicarbonate may be the treatment of choice in the prevention of contrast-induced nephropathy, because of less prescribed fluid volume and a lesser time required for infusion of the fluid.