A comparison of observed versus estimated baseline creatinine for determination of RIFLE class in patients with acute kidney injury

Methods. Data from the Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study, a prospective observational study from 54 ICUs in 23 countries of critically ill patients with severe AKI, were analysed. The RIFLE class was determined by using observed (o) pre-morbid and estimated (e) baseline SCr values. Agreement was evaluated by correlation coefficients and Bland-Altman plots. Sensitivity analysis by chronic kidney disease (CKD) status was performed. Results. Seventy-six percent of patients (n = 1327) had a pre-morbid baseline SCr, and 1314 had complete data for evaluation. Forty-six percent had CKD. The median (IQR) values were 97 mu mol/L (79-150) for oSCr and 88 mu mol/L (71-97) for eSCr. The oSCr and eSCr determined at ICU admission and at study enrolment showed only a modest correlation (r = 0.49, r = 0.39). At ICU admission and study enrolment, eSCr misclassified 18.8% and 11.7% of patients as having AKI compared with oSCr. Exclusion of CKD patients improved the correlation between oSCr and eSCr at ICU admission and study enrolment (r = 0.90, r = 0.84) resulting in 6.6% and 4.0% being misclassified, respectively. Conclusions. While limited, estimating baseline SCr by the MDRD equation when pre-morbid SCr is unavailable would appear to perform reasonably well for determining the RIFLE categories only if and when pre-morbid GFR was near normal. However, in patients with suspected CKD, the use of MDRD to estimate baseline SCr overestimates the incidence of AKI and should not likely be used. Improved methods to estimate baseline SCr are needed.

Is Coronary Artery Calcification Associated with Vertebral Bone Density in Nondialyzed Chronic Kidney Disease Patients?

Background and objectives Low bone mineral density and coronary artery calcification (CAC) are highly prevalent among chronic kidney disease (CKD) patients, and both conditions are strongly associated with higher mortality. The study presented here aimed to investigate whether reduced vertebral bone density (VBD) was associated with the presence of CAC in the earlier stages of CKD. Design, setting, participants, & measurements Seventy-two nondialyzed CKD patients (age 52 +/- 11.7 years, 70% male, 42% diabetics, creatinine clearance 40.4 +/- 18.2 ml/min per 1.73 m(2)) were studied. VBD and CAC were quantified by computed tomography. Results CAC > 10 Agatston units (AU) was observed in 50% of the patients (median 120 AU [interquartile range 32 to 584 AU]), and a calcification score >= 400 AU was found in 19% (736 [527 to 1012] AU). VBD (190 +/- 52 Hounsfield units) correlated inversely with age (r = -0.41, P < 0.001) and calcium score (r = -0.31, P = 0.01), and no correlation was found with gender, creatinine clearance, proteinuria, lipid profile, mineral parameters, body mass index, and diabetes. Patients in the lowest tertile of VBD had expressively increased calcium score in comparison to the middle and highest tertile groups. In the multiple logistic regression analysis adjusting for confounding variables, low VBD was independently associated with the presence of CAC. Conclusions Low VBD was associated with CAC in nondialyzed CKD patients. The authors suggest that low VBD might constitute another nontraditional risk factor for cardiovascular disease in CKD. Clin J Am Soc Nephrol 6: 1456-1462, 2011. doi: 10.2215/CJN.10061110

Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury

Purpose: The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes. Methods: This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients. Results: Timing of RRT was stratified into ""early"" and ""late"" by median urea and creatinine at the time RRT was started. Timing was also categorized temporally from ICU admission into early (<2 days), delayed (2-5 days), and late (>5 days). Renal replacement therapy timing by serum urea showed no significant difference in crude (63.4% for urea <= 24.2 mmol/L vs 61.4% for urea >24.2 mmol/L; odds ratio [OR], 0.92; 95% confidence interval [CI], 0.73-1.15; P = .48) or covariate-adjusted mortality (OR, 1.25; 95% CI, 0.91-1.70; P = .16). When stratified by creatinine, late RRT was associated with lower crude (53.4% for creatinine >309 mu mol/L vs 71.4% for creatinine <= 309 mu mol/L; OR, 0.46; 95% CI, 0.36-0.58; P < .0001) and covariate-adjusted mortality (OR, 0.51; 95% CI, 0.37-0.69; P < .001).However, for timing relative to ICU admission, late RRT was associated with greater crude (72.8% vs 62.3% vs 59%, P < .001) and covariate-adjusted mortality (OR, 1.95; 95% CI, 1.30-2.92; P = .001). Overall, late RRT was associated with a longer duration of RRT and stay in hospital and greater dialysis dependence. Conclusion: Timing of RRT, a potentially modifiable factor, might exert an important influence on patient survival. However, this largely depended on its definition. Late RRT (days from admission) was associated with a longer duration of RRT, longer hospital stay, and higher dialysis dependence. (C) 2009 Elsevier Inc. All rights reserved.

Urine Volume in Acute Kidney Injury: How Much Is Enough?

Eight hundred and seventy-nine patients with acute kidney injury were retrospectively studied over year and eleven months for evaluation of urine volume as a risk factor for death. They were divided into five groups, according to the 24 h urine volume (UV): anuric (UV <= 50 mL/24 h, group 1), oliguric (UV > 50 mL/24 h and < 400 mL/24 h, group 2), and non-oliguric (UV >= 400 mL/24 h). Nonoliguric group was subdivided in three subgroups: UV > 400 mL/24 h and <= 1000 mL/24 h (group 3, reference group), UV > 1000 mL/24 h and <= 2000 mL/24 h (group 4), and UV > 2000 mL/24 h (group 5). Linear tendency test (Mantel extension) pointed out a significant increase in mortality with UV decrease (p < 0.001), confirmed by multivariate analysis. Anuric and oliguric patients had increased risk of respectively 95% and 76% times for death compared to controls (p < 0.05). Patients from groups 4 and 5 presented a reduced risk for death of 50% and 70%, respectively, p = 0.004 and p = 0.001. In conclusion, urine volume was a strong independent factor for mortality in this cohort of AKI patients.

Fluoxetine effect on kidney water reabsorption

Background. The pathogenesis of hyponatraemia caused by fluoxetine (Fx) use in the treatment of depression is not well understood. It has been attributed to a SIADH, although ADH-enhanced plasma level has not yet been demonstrated in all the cases reported in humans. This experiment aimed at investigating the effect of fluoxetine on the kidney and more specifically in the inner medullary collecting duct (IMCD). Methods. ( 1) In vivo study: ( a) 10 rats were injected daily i. p. with 10 mg/kg fluoxetine doses. After 10 days, rats were sacrificed and blood and kidneys were collected. (b) Immunoblotting studies for AQP2 protein expression in the IMCD from injected rats and in IMCD tubules suspension from 10 normal rats incubated with 10(-7) M fluoxetine. ( 2) In vitro microperfusion study: The osmotic water permeability (P-f, mu m/s) was determined in normal rats IMCD (n = 6), isolated and perfused by the standard methods. Results. In vivo study: ( a) Injected rats with fluoxetine lost about 12% body weight; Na+ plasma level decreased from 139.3 +/- 0.78 mEq/1 to 134.9 +/- 0.5 mEq/1 ( p < 0.01) and K+ and ADH plasma levels remained unchanged. ( b) Immunoblotting densitometric analysis of the assays showed an increase in AQP2 protein abundance of about 40%, both in IMCDs from injected rats [ control period (cont) 99.6 +/- 5.2 versus Fx 145.6 +/- 16.9, p < 0.05] and in tubule suspension incubated with fluoxetine ( cont 100.0 +/- 3.5 versus 143.0 +/- 2.0, p < 0.01). In vitro microperfusion study fluoxetine increased Pf in the IMCD in the absence of ADH from the cont 7.24 +/- 2.07 to Fx 15.77 +/- 3.25 ( p < 0.01). Conclusion. After fluoxetine use, the weight and plasma Na+ level decreased, and the K+ and ADH plasma levels remained unchanged, whereas the AQP2 protein abundance and water absorption in the IMCD increased, leading us to conclude that the direct effect of fluoxetine in the IMCD could explain at least in part, the hyponatraemia found sometime after this drug use in humans.

Impact of mild acute kidney injury (AKI) on outcome after open repair of aortic aneurysms

Recently, mild AKI has been considered as a risk factor for mortality in different scenarios. We conducted a retrospective analysis of the risk factors for two distinct definitions of AKI after elective repair of aortic aneurysms. Logistic regression was carried out to identify independent risk factors for AKI ( defined as >= 25% or >= 50% increase in baseline SCr within 48 h after surgery, AKI 25% and AKI 50%, respectively) and for mortality. Of 77 patients studied ( mean age 68 +/- 10, 83% male), 57% developed AKI 25% and 33.7% AKI 50%. There were no differences between AKI and control groups regarding comorbidities and diameter of aneurysms. However, AKI patients needed a supra-renal aortic cross-clamping more frequently and were more severely ill. Overall in-hospital mortality was 27.3%, which was markedly higher in those requiring a supra-renal aortic cross-clamping. The risk factors for AKI 25% were suprarenal aortic cross-clamping ( odds ratio 5.51, 95% CI 1.05-36.12, p = 0.04) and duration of operation for AKI 25% ( OR 6.67, 95% CI 2.23-19.9, p < 0.001). For AKI 50%, in addition to those factors, post-operative use of vasoactive drugs remained as an independent factor ( OR 6.13, 95% CI 1.64-22.8, p = 0.005). The risk factors associated with mortality were need of supra-renal aortic cross-clamping ( OR 9.6, 95% CI 1.37-67.88, p = 0.02), development of AKI 50% ( OR 8.84, 95% CI 1.31-59.39, p = 0.02), baseline GFR lower than 49 mL/min ( OR 17.07, 95% CI 2.00 145.23, p = 0.009), and serum glucose > 118 mg/dL in the post-operative period ( OR 19.99, 95% CI 2.32-172.28, p = 0.006). An increase of at least 50% in baseline SCr is a common event after surgical repair of aortic aneurysms, particularly when a supra-renal aortic cross-clamping is needed. Along with baseline moderate chronic renal failure, AKI is an independent factor contributing to the high mortality found in this scenario.

Neutrophil depletion increases susceptibility to systemic and vaginal candidiasis in mice, and reveals differences between brain and kidney in mechanisms of host resistance

Infections caused by the yeast Candida albicans represent an increasing threat to debilitated and immunosuppressed patients, and neutropenia is an important risk factor. Monoclonal antibody depletion of neutrophils in mice was used to study the role of these cells in host resistance. Ablation of neutrophils increased susceptibility to both systemic and vaginal challenge. The fungal burden in the kidney increased threefold on day 1, and 100-fold on day 4, and infection was associated with extensive tissue destruction. However, a striking feature of the disseminated disease in neutrophil-depleted animals was the altered pattern of organ involvement. The brain, which is one of the primary target organs in normal mice, was little affected. There was a threefold increase in the number of organisms recovered from the brains of neutrophil-depleted mice on day 4 after infection, but detectable abscesses were rare. In contrast, the heart, which in normal mice shows only minor lesions, developed severe tissue damage following neutrophil depletion. Mice deficient in C5 demonstrated both qualitative and quantitative increases in the severity of infection after neutrophil depletion when compared with C5-sufficient strains. The results are interpreted as reflecting organ-specific differences in the mechanisms of host resistance.

When Should Renal Replacement Therapy be Initiated for Acute Kidney Injury?

Acute kidney injury (AKI) is now well recognized as an independent risk factor for increased morbidity and mortality particularly when dialysis is needed. Although renal replacement therapy (RRT) has been used in AKI for more than five decades, there is no standard methodology to predict which AKI patients will need dialysis and who will recover renal function without requiring dialysis. The lack of consensus on what parameters should guide the decision to start dialysis has led to a wide variation in dialysis utilization. A contributing factor is the lack of studies in the modern era evaluating the relationship of timing of dialysis initiation and outcomes. Although listed as one of the top priorities in research on AKI, timing of dialysis initiation has not been included as a factor in large, randomized controlled trials in this area. In this review we will discuss the criteria that have been used to define early vs. late initiation in previous studies on dialysis initiation. In addition, we propose a patient-centered approach to define early and late initiation that could serve as framework for managing patients and for future studies in this area.

Carbamazepine can induce kidney water absorption by increasing aquaporin 2 expression

Background. Carbamazepine (Carba) is an anticonvulsant and psychotropic drug used widely for the treatment of intellectual disability and severe pains, but the incidence of hyponatremia is a common related occurrence. This hyponatremia is frequently attributed to a SIADH induced by this drug. It is also known that Carba is used to decrease the urinary volume in Diabetes Insipidus (DI) because it has an antidiuretic effect. Lithium (Li) is one of the most important drugs used to treat bipolar mood disorders. However Li has the undesirable capacity to induce DI. Nowadays, the association of these drugs is used in the treatment of patients with psychiatric and neurological problems. Methods. In vivo and in vitro (microperfusion) experiments were developed to investigate the effect of Carba in the rat Inner Medullary Collecting Duct (IMCD). Results. The results revealed that Carba was able to stimulate the V2 vasopressin receptor-Protein G complex increasing the water permeability (Pf) and water absorption. In vivo studies showed that in rats with lithium-induced DI, Carba decreased the urinary volume and increased the urinary osmolality. AQP2 expression was increased both in normal IMCD incubated with Carba and in IMCD from lithium-induced DI after Carba addition to the diet, when compared with the control. Conclusion. These results showed that the hyponatremia observed in patients using this anticonvulsant drug, at least in part, is due to the Carba capacity to increase IMCD`s Pf and that the Lithium-Carbamazepine association is beneficial to the patient.

Transurethral injection therapy with carbon-coated beads (Durasphere (R)) for treatment of recurrent pyelonephritis in kidney transplant patients with vesico-ureteral reflux to the allograft

Introduction and objectives: Recurrent transplant pyelonephritis (RTP) secondary to vesico-ureteral reflux (VUR) to the transplant kidney (KTx) remains a significant cause of infectious complications with impact on patient and graft outcomes. Our objective was to verify the safety and efficacy of transurethral injection of Durasphere (R) to relieve RTP secondary to VUR after renal transplantation. Patients and methods: Between June 2004 and July 2008, eight patients with RTP (defined as two or more episodes of pyelonephritis after transplantation) and VUR to the KTx were treated with subureteral injections of Durasphere (R). The mean age at surgery was 38.8 +/- 13.8 yr (23-65). The patients were followed regularly every six months. The mean interval between the KTx and the treatment was 76 +/- 74.1 (10-238 months). The mean follow-up was 22.3 +/- 16.1 months (8-57 months). Results: Six patients (75%) were free of pyelonephritis during a mean period of follow-up of 23.2 +/- 17.1 months (8-57 months). Two of them had no VUR and four cases presented with G II VUR (pre-operative G IV three cases and one case G III). In one case, symptomatic recurrent cystitis made a second treatment necessary. This patient remained free of infections for three yr after the first treatment and for 18 months after the second treatment. Of the remaining two patients, one had six episodes of RTP before treatment in a period of three yr and only two episodes after treatment in two yr of follow-up. The last case had a new episode of pyelonephritis five months after treatment. Conclusions: Transurethral injection therapy with Durasphere (R) is a safe and effective minimally invasive treatment option for KTx patients with recurrent RTP. A second treatment seems to be necessary in some cases.

Mesenchymal Stem Cells Delivered at the Subcapsule of the Kidney Ameliorate Renal Disease in the Rat Remnant Kidney Model

Stem cells (SC) are potential therapeutic tools in the treatment of chronic renal diseases. Number and engraftment of SC in the injured sites are important for possible differentiation into renal cells and paracrine effect. The aim of this study was to analyze the effect of subcapsular injection of mesenchymal stem cells (MSC) in the 5/6 nephrectomy model (5/6 Nx). MSC obtained from Wistar rats were isolated by their capacity to adhere to plastic surfaces, characterized by flow cytometry, and analyzed by their differentiation potential into osteoblasts. MSC (2 X 105) were injected into the subcapsule of the remnant kidney of male Wistar rats, and were followed for 15 or 30 days. 5/6 Nx rats showed significant hypertension at 15 and 30 days, which was reduced by MSC at 30 days. Increased albuminuria and serum creatinine at 15 and 30 days in 5/6 Nx rats were also reduced by subcapsular injection of MSC. We also observed a significant reduction of glomerulosclerosis index 30 days after injection of MSC. 4-6 diamidino-2-phenylindole dihydrochloride (DAPI)-stained MSC showed a migration of these cells into renal parenchyma 5, 15, and 30 days after subcapsular injection. In conclusion, our data demonstrated that subcapsular injection of MSC in 5/6 Nx rats is associated with renoprotective effects. These results suggest that locally implanted MSC in the kidney allow a large number of cells to migrate into the injured sites and demonstrate that subcapsular injection represent an effective route for MSC delivery.

Conversion to Sirolimus in Kidney-Pancreas and Pancreas Transplantation

Reports on the use of sirolimus (SRL) in pancreas transplantation are still limited. The aim of this study was to evaluate the outcome of SRL conversion in pancreas transplant patients. Among 247 patients undergoing simultaneous kidney-pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL. The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity (n = 24; 73%), severe neurotoxicity owing to CNI (n = 1; 3%), severe and/or recurrent acute rejection episodes (n = 7; 21.%), gastrointestinal (GI) side effects of mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia (n = 4; 12%). Before conversion, all patients were maintained on a CNI, MMF, and low-dose steroids. They were gradually converted to SRL associated with either CNI or MMF withdrawal. Sixty-three percent (n = 15) of patients who were converted owing to CNI nephrotoxicity, showed stable or improved renal function. At 12 months after conversion, serum creatinine levels were significantly decreased in this group (2.2 +/- 0.5 vs 1.6 +/- 0.3 mg/dL; P = .001) and C-peptide values increased (2.9 +/- 1.1.1 vs 3.1 +/- 1.3 nmol/L; P = .01.8). The only patient with leucoencephalopathy showed improved neurologic status after SRL conversion. All patients converted to SRL because of GI side effects of MMF showed improvements, and none of those converted because of hyperglycemia experienced improvement. There were no episodes of acute rejection after conversion. We concluded that conversion to SRL in pancreas transplantation should be considered an important alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and in cases of severe diarrhea due to MMF.

Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial

Creatine supplementation may have a therapeutic role in diabetes, but it is uncertain whether this supplement is safe for kidney function. The aim of this study was to investigate the effects of creatine supplementation on kidney function in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial was performed. The patients were randomly allocated to receive either creatine or placebo for 12 weeks. All the patients underwent exercise training throughout the trial. Subjects were assessed at baseline and after the intervention. Blood samples and 24-h urine samples were obtained for kidney function assessments. Additionally, (51)Cr-EDTA clearance was performed. To ensure the compliance with creatine intake, we also assessed muscle phosphorylcreatine content. The creatine group presented higher muscle phosphorylcreatine content when compared to placebo group (CR Pre 44 +/- A 10, Post 70 +/- A 18 mmol/kg/wt; PL Pre 52 +/- A 13, Post 46 +/- A 13 mmol/kg/wt; p = 0.03; estimated difference between means 23.6; 95% confidence interval 1.42-45.8). No significant differences were observed for (51)Cr-EDTA clearance (CR Pre 90.4 +/- A 16.9, Post 96.1 +/- A 15.0 mL/min/1.73 m(2); PL Pre 97.9 +/- A 21.6, Post 96.4 +/- A 26.8 mL/min/1.73 m(2); p = 0.58; estimated difference between means -0.3; 95% confidence interval -24.9 to 24.2). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria were unchanged. CR supplementation does not affect kidney function in type 2 diabetic patients, opening a window of opportunities to explore its promising therapeutic role in this population. ClinicalTrials.gov registration number: NCT00992043.

Peritoneal Dialysis in Acute Kidney Injury: Lessons Learned and Applied

Peritoneal dialysis (PD) is a simple, safe, gentle, and efficient renal replacement therapy (RRT) method. It is able to correct acute kidney injury (AKI)-induced metabolic, electrolytic, and acid-base disorders and volume overload both in and out the intensive care unit setting. Some PD modalities, such as high-volume PD and continuous flow PD, can provide RRT doses and efficiency comparable to extracorporeal blood purification methods. PD is particularly suitable for children, patients with refractory heart failure or hemodynamically instable, conditions where systemic anticoagulation should be avoided, patients with difficulty for vascular access and hypo- and hyperthermia conditions. In the following manuscript, PD technical aspects and the possible advantages and limitations of this RRT method will be discussed, and the more recent literature on clinical experience with PD for treatment of AKI will be reviewed.