A challenging diagnosis of reversible "vascular" dementia: Cerebral amyloid angiopathy-related inflammation.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare and treatable variant of CAA likely due to an autoimmune response directed toward beta-amyloid deposits. Cognitive and behavioral manifestations are the most common symptoms, followed by focal neurological signs, headache and seizures, associated with characteristics neuroradiological features on brain magnetic resonance imaging (MRI). We describe the clinical course, radiological features and therapeutic approach of two patients with probable CAA-ri with the aim of emphasizing the importance of an early diagnosis of this potentially reversible disease in different neurological settings, such as memory clinics and stroke units.

Sex Differences in the Relationship between PTSD Spectrum Symptoms and Autistic Traits in a Sample of University Students.

BACKGROUND: While growing literature is stressing the link between Autistic Traits (AT) and trauma-/stress-related disorders, in both conditions significant differences have been separately reported. OBJECTIVE: This study aims to evaluate the relationship between AT and trauma-/stress-related symptoms with respect to sex. METHODS: 178 university students were assessed with the Structured Clinical Interview for DSM-5, the Trauma and Loss Spectrum (TALS) and the Adult Autism Subthreshold Spectrum (AdAS). In order to evaluate sex differences in trauma-/stress-related symptoms among subjects with higher or lower AT, the sample was split in two groups with an equal number of subjects on the basis of the median score reported on AdAS Spectrum ("AdAS high scorers" and "AdAS low scorers"). RESULTS: Females reported significantly higher TALS total score, Loss events and Grief reaction domain scores than males in the whole sample, while AdAS high scorers reported significantly higher TALS total and domain scores than AdAS low scorers. A significant interaction between high/low AdAS score and sex emerged for TALS domains, with females scoring significantly higher than males only among AdAS low scorers, specifically on Loss events, Grief reaction, Re-experiencing and Personal characteristics/Risk factors domains. Finally, among AdAS high scorers a significantly higher rate of subjects fulfilled symptomatological criteria for PTSD than among AdAS low scorers, without sex differences. CONCLUSION: Our results confirm a significant relationship between AT and trauma-/stress-related symptoms, which seems to prevail on sex differences among high-risk subjects.

Long-term Glomerular Filtration Rate and Kidney Disease: Improving Global Outcomes Stage Stability After Conversion to Once-Daily Tacrolimus in Kidney Transplant Recipients.

Close monitoring of estimated glomerular filtration rate (eGFR) is important for early recognition of worsening renal function to prevent further deterioration. Safe conversion from twice-daily tacrolimus (TD-Tac) to once-daily tacrolimus (OD-Tac) has been reported, but the effects on eGFR are contrasting. The aim of our study is to evaluate long-term stability of eGFR after 1:1 conversion from TD-Tac to OD-Tac and the effects on serum cytokine blood levels. Forty-six consecutive kidney transplant recipients treated with TD-Tac 3 to 5 years post-transplant, with stable renal function, were enrolled in the study (2009-2011). Clinical and biochemical parameters were evaluated for 12 months before conversion up to 6 years after conversion. The patients served as their own controls. A panel of cytokines was evaluated repeatedly during the first year after conversion. Mean values of eGFR were not different long-term after conversion (P = .11) compared with baseline, and the majority of patients remained stable on Kidney Disease: Improving Global Outcomes stage during the study period; eGFR was stable in 30.0% after 5 years, decreased > 1 mL/min/1.73 m2/y in 13.3%, and improved > 1 mL/min/1.73 m2/y in 56.7%. Cytokine levels and C-reactive protein did not show any significant deterioration. Metabolic parameters were stable during the 6 years of follow-up. OD-Tac therapy can preserve an effective immunosuppressive state together with a safe profile of eGFR.

Surgical Technique Notes of Arterial Vascular Reconstruction During Kidney Transplantation: Personal Experience and Literature Review.

BACKGROUND: Arterial vascular anomalies in patients undergoing kidney transplantation (KT) are correlated with a higher incidence of early surgical complications, potentially causing graft loss. Arterial reconstruction allows patients to overcome these surgical challenges, thus minimizing the risk of poor outcomes. The aim of the present study is to retrospectively investigate the safety and effectiveness of the multiple arterial reconstruction technique with a Teflon patch in case of an unavailable aortic patch: to do so, surgical complications, graft function, and patient survival were evaluated. METHODS: During the period January 2009 to August 2016, 202 adult deceased-donor KTs were performed at our center. Group A (n = 27; reconstruction of multiple arteries) and Group B (n = 175; control group) were compared. RESULTS: No differences were observed between the 2 groups in terms of early postoperative course, with no vascular complication observed in Group A. No vascular patch infections were reported, nor longer cold ischemia time rates. Similarly, long-term survival rates were similar between the 2 groups. CONCLUSIONS: The Teflon-patch arterial reconstruction technique appears to be safe and effective, with an acceptable balance of benefits and potential risks of using a prosthetic material. Studies based on larger series are needed to further validate this approach.

Automated Intelligent Microscopy for the Recognition of Decoy Cells in Urine Samples of Kidney Transplant Patients.

BACKGROUND: BK virus (BKV)-associated nephropathy is definitely involved in allograft failure after kidney transplant. Thus, the need for an early control of viral reactivation in immunocompromised patients is well established. Determination of urinary release of decoy cells (DC) and BK viral load in plasma and urine by polymerase chain reaction (PCR) usually precedes renal biopsy. The aim of the study is to assess viral reactivation by BKV-DNA PCR and DC detection in urinary sediment using automated intelligent microscopy. METHODS: Seventy-eight kidney transplant patients were analyzed for the presence of plasma BKV-DNA by quantitative TaqMan real-time PCR. Additionally, automated intelligent microscopy was used for urine sediment analysis, allowing to count cells with decoy feature, confirmed by phase contrast microscopic review. RESULTS: Plasma BKV-DNA PCR was detected in 14 (17.9%) patients. DC were identified in 19 (24.3%) urine sediments by automated analyzers and confirmed by microscopic observation. Two patients were BKV-DNA-positive/DC-negative; conversely, 7 subjects were DC-positive/BKV-DNA-negative. CONCLUSIONS: Plasma quantification of BK viral load is currently the best noninvasive method for the detection of viral reactivation. Nevertheless, automated methods to screen for the presence of DC in urine could facilitate early BK virus replication diagnosis and patient follow-up by quantitative and visual results.

Pre-Emptive Therapy for the Treatment of Cytomegalovirus After Kidney Transplantation.

BACKGROUND: Cytomegalovirus (CMV) represents the leading cause of viral infection in kidney transplantation patients. The aim of the present study was to evaluate the efficacy and safety of pre-emptive anti-CMV therapy. MATERIALS AND METHODS: We performed a retrospective analysis based on data from 227 consecutive patients transplanted from 2010 to 2015, of whom 38 (16.6%) were from a living donor, considering: incidence of rejection, CMV organ localization, and graft and patient survival. All patients underwent induction immunosuppressive therapy followed by maintenance therapy consisting of corticosteroids, antimetabolites, and tacrolimus (median basal dose = 5.3 ng/mL). The timing for the detection of plasma CMV-DNA in the post-transplantation period was: weekly (first month), quarterly (second through twelfth month), and then half-yearly. RESULTS: CMV viremia was positive in 98 of 227 (43.1%) patients, with an average of 248,482 copies/mL (range: 250 copies/mL to 9,745,000 copies/mL) and the first positivity after a median period of 2.5 months from kidney transplantation (range: 0.2 months to 43 months). A total of 49 of 227 (21.5%) patients were treated with antivirals: 27 of 49 (55.1%) because of CMV organ localization (gastrointestinal = 20, lungs = 3, kidney = 2, liver = 2). Fourteen of 227 (6.1%) patients had a rejection episode, 7 (3.1%) of which were CMV-related. Fifteen of 227 (6.6%) patients died (noninfectious CMV-related complications = 8, cardiovascular causes = 6, bleeding complications = 1). CONCLUSION: Our experience confirms the validity of the pre-emptive anti-CMV therapy in renal transplantation patients.

Kidney Transplantation in Alström Syndrome: Case Report.

The Alström syndrome is a rare genetic disorder, inherited in an autosomal recessive manner. It has recently been classified as a ciliopathic disorder. Alström syndrome is a multiorgan pathology characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dyslipidemia, short stature in adulthood, hypothyroidism, hypogonadism, dilated or restrictive cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. End-stage renal disease can occur as early as the late teens and is the leading cause of death. More than 900 people with Alström syndrome have been reported worldwide. We present a case of a 42-year-old man affected by this syndrome with end-stage renal disease, type 2 diabetes mellitus, and loss of visual function and hearing who received a kidney transplant from a cadaveric donor. Basiliximab and steroid were used as induction therapy. Tacrolimus, mycophenolate mofetil, and steroid were used as maintenance therapy. No complications were reported during the recovery. In selected patients affected by Alström syndrome, renal transplantation can be a successful treatment for chronic kidney disease.

A systematic review of cognitive effects of exercise in depression.

OBJECTIVE: The aim of the present systematic review and meta-analysis was to evaluate the impact of physical exercise on cognitive symptoms in depressed adult patients. METHODS: Systematic literature search was performed in Web of Science™ and CINAHL from inception to August 2016. Two reviewers independently selected randomized trials evaluating the effect of exercise on cognitive functions in patients with a validated diagnosis of depression. Outcome measures included global cognition and different cognitive domains (speed of processing, attention/vigilance, working memory, verbal and visual memory, and reasoning). RESULTS: Eight trials met inclusion criteria (637 patients). A fixed-effects model showed absence of beneficial effect on global cognition (Hedges' g = 0.07, 95% CI -0.08 to 0.24, I2  = 0%) as well as on specific cognitive domains. Sensitivity analyses did not show an impact of exercise in studies with shorter intervention duration compared to longer trials (between group heterogeneity Q = 3.564, df = 1, P = 0.059), single session per week compared to multiple sessions (Q = 2.691, df = 1, P = 0.101) and low exercise intensity compared with moderate/high intensity (Q = 2.952, df = 1, P = 0.086). CONCLUSION: Our meta-analysis did not observe a substantial benefit of physical exercise on cognitive symptoms in depression.

Is aceruloplasminemia treatable? Combining iron chelation and fresh-frozen plasma treatment.

We report the case of a patient with hereditary ceruloplasmin deficiency due to a novel gene mutation in ceruloplasmin gene (CP), treated with fresh frozen plasma (FFP) and iron chelation therapy. A 59-year-old man with a past history of diabetes was admitted to our department due to progressive gait difficulties and cognitive impairment. Neurological examination revealed a moderate cognitive decline, with mild extrapyramidal symptoms, ataxia, and myoclonus. Brain T2-weighted MR imaging showed bilateral basal ganglia hypointensity with diffuse iron deposition. Increased serum ferritin, low serum copper concentration, undetectable ceruloplasmin, and normal urinary copper excretion were found. The genetic analysis of the CP (OMIM #604290) reported compound heterozygosity for two mutations, namely c.848G > A and c.2689_2690delCT. Treatment with FFP (500 mL i.v./once a week) and administration of iron chelator (Deferoxamine 1000 mg i.v/die for 5 days, followed by Deferiprone 500 mg/die per os) were undertaken. At the 6-month follow-up, clinical improvement of gait instability, trunk ataxia, and myoclonus was observed; brain MRI scan showed no further progression of basal ganglia T2 hypointensity. This case report suggests that the early initiation of combined treatment with FFP and iron chelation may be useful to reduce the accumulation of iron in the central nervous system and to improve the neurological symptoms.

Prognostic significance of proteinuria in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: Proteinuria and estimated glomerular filtration rate (eGFR) are indicators of renal function. Whether proteinuria better predicts outcome than eGFR in stroke patients treated with intravenous thrombolysis (IVT) remains to be determined. METHODS: In this explorative multicenter IVT register based study, the presence of urine dipstick proteinuria (yes/no), reduced eGFR (<60 ml/min/1.73 m2 ) and the coexistence of both with regard to (i) poor 3-month outcome (modified Rankin Scale score 3-6), (ii) death within 3 months and (iii) symptomatic intracranial hemorrhage (ECASS-II criteria) were compared. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals were calculated. RESULTS: Amongst 3398 patients, 881 (26.1%) had proteinuria and 623 (18.3%) reduced eGFR. Proteinuria [ORadjusted 1.65 (1.37-2.00) and ORadjusted 1.52 (1.24-1.88)] and reduced eGFR [ORadjusted 1.26 (1.01-1.57) and ORadjusted 1.34 (1.06-1.69)] were independently associated with poor functional outcome and death, respectively. After adding both renal markers to the models, proteinuria [ORadjusted+eGFR 1.59 (1.31-1.93)] still predicted poor outcome whilst reduced eGFR [ORadjusted+proteinuria 1.20 (0.96-1.50)] did not. Proteinuria was associated with symptomatic intracranial hemorrhage [ORadjusted 1.54 (1.09-2.17)] but not reduced eGFR [ORadjusted 0.96 (0.63-1.62)]. In 234 (6.9%) patients, proteinuria and reduced eGFR were coexistent. Such patients were at the highest risk of poor outcome [ORadjusted 2.16 (1.54-3.03)] and death [ORadjusted 2.55 (1.69-3.84)]. CONCLUSION: Proteinuria and reduced eGFR were each independently associated with poor outcome and death but the statistically strongest association appeared for proteinuria. Patients with coexistent proteinuria and reduced eGFR were at the highest risk of poor outcome and death.

Impact of body mass index on outcome in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: The impact of body mass index (BMI) on outcome in stroke patients treated with intravenous thrombolysis (IVT) was investigated. METHODS: In a multicentre IVT-register-based observational study, BMI with (i) poor 3-month outcome (i.e. modified Rankin Scale scores 3-6), (ii) death and (iii) symptomatic intracranial haemorrhage (sICH) based on criteria of the ECASS II trial was compared. BMI was used as a continuous and categorical variable distinguishing normal weight (reference group 18.5-24.9 kg/m2 ) from underweight (<18.5 kg/m2 ), overweight (25-29.9 kg/m2 ) and obese (≥30 kg/m2 ) patients. Univariable and multivariable regression analyses with adjustments for age and stroke severity were done and odds ratios with 95% confidence intervals [OR (95% CI)] were calculated. RESULTS: Of 1798 patients, 730 (40.6%) were normal weight, 55 (3.1%) were underweight, 717 (39.9%) overweight and 295 (16.4%) obese. Poor outcome occurred in 38.1% of normal weight patients and did not differ significantly from underweight (45.5%), overweight (36.1%) and obese (32.5%) patients. The same was true for death (9.5% vs. 14.5%, 9.6% and 7.5%) and sICH (3.9% vs. 5.5%, 4.3%, 2.7%). Neither in univariable nor in multivariable analyses did the risks of poor outcome, death or sICH differ significantly between BMI groups. BMI as a continuous variable was not associated with poor outcome, death or sICH in unadjusted [OR (95% CI) 0.99 (0.97-1.01), 0.98 (0.95-1.02), 0.98 (0.94-1.04)] or adjusted analyses [OR (95% CI) 1.01 (0.98-1.03), 0.99 (0.95-1.05), 1.01 (0.97-1.05)], respectively. CONCLUSION: In this largest study to date, investigating the impact of BMI in IVT-treated stroke patients, BMI had no prognostic meaning with regard to 3-month functional outcome, death or occurrence of sICH.

Impulse control disorder in PD: A lateralized monoaminergic frontostriatal disconnection syndrome?

BACKGROUND: Impulse Control Disorder symptoms (ICD) in Parkinson's disease (PD) has been recently associated by magnetic Resonance imaging with impaired cortico-striatal connectivity, especially between left putamen and frontal associative areas. METHODS: 84 patients entered the study (21 PD-ICD+ and 64 PD-ICD-) and underwent DATSCAN imaging. The striatal tracer uptake was evaluated using BRASS software (Hermes, Sweden). The whole-brain analysis was performed with Statistical Parametric Mapping (SPM). RESULTS: PD-ICD+ showed a significant reduction of left putaminal and left inferior frontal gyrus tracer uptake compared to PD-ICD-. Functional covariance analysis using left putamen as the seed point showed that, in contrast to ICD-patients, ICD+ patients had no functional covariance with contralateral basal ganglia and ipsilateral cingulate cortex, as index of an impaired inter- and intra-hemispheric dopamine binding in PD-ICD+. DISCUSSION: the results support and expand the concept of a functional disconnection syndrome linked to ICD symptoms in PD patients through an asymmetric molecular frontostriatal network breakdown with left basal ganglia as central hub.

Delayed Introduction of Everolimus in De Novo Renal Transplanted Patients: A Single-Center Experience.

INTRODUCTION: Immunosuppressive protocols containing everolimus (EVR) preserve good renal function in kidney transplantation (KT), although they are often complicated by several adverse events. We have evaluated the efficacy and safety of a protocol with late (1 month after KT) EVR introduction. MATERIAL AND METHODS: This study randomized 49 de novo patients undergoing KT between September 2012 and June 2014 into 2 groups: group A (n = 24) with late EVR introduction and tacrolimus reduction, and group B (control group; n = 25) with a standard immunosuppressive regimen. Primary aims were 1-year patient and graft survivals and acute rejection rates. Secondary aims were related to wound, metabolic, and hematologic complications. RESULTS: Patient and graft survivals were similar in both groups. One year after KT, median serum creatinine was inferior in group A (1.4 vs 1.8 mg/dL; P = .004). Late acute rejection (8.3 vs 12.0%; P = 1.0) and wound complication (4.2 vs 4.0%; P = 1.0) rates were similar. Higher cholesterol and triglycerides and lower platelets and hemoglobin levels were observed in group A. CONCLUSIONS: In our experience, delayed introduction of EVR shows similar results with respect to its early introduction, contemporaneously presenting fewer wound complications and lymphoceles. A higher rate of metabolic and hematologic complications are, however, observed in patients under EVR therapy. Further multicenter studies should be performed to confirm these preliminary results.

Adacolumn Granulocyte-Apheresis for Alcoholic Hepatitis: Preliminary Study.

INTRODUCTION: Alcoholic hepatitis (AH) is an acute-on-chronic inflammatory response affecting the liver. It has been recognized that white blood cells (WBCs) are involved in the pathogenesis and in the prognosis of AH. The aim of study was to use Adacolumn, which can selectively adsorb myeloid linage leucocytes (granulocytes and monocytes/macrophages) from the blood in the column and improve the clinical status of patients. MATERIALS: Six patients with a diagnosis of AH were treated with Adacolumn granulocyte-apheresis therapy. INCLUSION CRITERIA: patients not responders to corticosteroids therapy with Maddrey Discriminant Function (MDF) >32 and MELD score 20-26. The patients underwent five 1-hour sessions for 5 consecutive days with a follow-up at 28 days. The column was placed in an extracorporeal setting with a perfusion rate of 30 mL/min and a duration of 60 minutes. Liver parameters, WBC count, proinflammatory cytokines, coagulation, and predictive scores were valued before and after the cycle of apheresis treatment. RESULTS: After 5 days, the findings showed a significant improvement of WBC count (P < .014) and cytokines such as interleukin (IL)-6 (P < .019), tumor necrosis factor α (TNFα) (P < .02), and IL-8 (P < .029). The results probably determined a reduction of aspartate transaminase (AST; P < .02) and alanine transaminase (ALT; P < .011), although we did not observe a significant improve in bilirubin, prothrombin time (PT), and Maddrey score. The improvement of MELD score, depending on an improvement of international normalized ratio for administration of plasma, was not considered. At day 28 of follow-up, PT, IL-6, TNFα, AST and ALT results significantly improved. CONCLUSIONS: The Adacolumn apheresis was safe and was able to determine an improvement of clinical status of patients with reduction of inflammatory markers. More patients are needed to validate these results.

Multiple Organ Failure Associated With Coxsackie Virus in a Kidney Transplant Patient: Case Report.

INTRODUCTION: Viral myocarditis can emerge with various symptoms, including fatal arrhythmia and cardiogenic shock, potentially evolving in chronic myocarditis or dilatative cardiomyopathy. We report a case of a kidney transplant patient affected by coxsackie viral myocarditis. METHODS: A 49-year-old man was admitted to our hospital with dyspnea and fever in August 2014. He underwent living donor kidney transplantation in 1986 and polar graft resection for papillary carcinoma in 2012. RESULTS: The initial investigation showed pulmonary congestion, pancreatitis, increased serum troponin I, and increased liver enzyme levels. Echocardiogram revealed an ejection fraction (EF) of 20% and PAPS 45 mm Hg. He underwent coronary stent implantation, started hemodialysis, and continued on low-dose steroid immunosuppressive therapy. The clinical course improved rapidly, but endomyocardial biopsy showed acute myocarditis. Further investigation revealed a high antibody titer against coxsackievirus B4 and B5. Pancreatic enzyme levels normalized 2 months after patient admission; his cardiac condition improved after 6 months. The patient has been followed for 1 year, and his left ventricular EF is stable (45%). CONCLUSIONS: Viral myocarditis represents a serious clinical condition requiring a fast therapeutic intervention. This patient's clinical course suggests that changes in his immunosuppressive therapy were associated with progressive amelioration of his viral myocarditis.

Plasmapheresis, Photopheresis, and Endovenous Immunoglobulin in Acute Antibody-mediated Rejection in Kidney Transplantation.

INTRODUCTION: Acute antibody-mediated rejection (AAMR) is the subject of much research. It is diagnosed by C4d staining at biopsy and circulating donor-specific antibodies (DSA). The combination of intensive plasmapheresis and intravenous immunoglobulin (IVIG) has been recognized as an effective treatment for AAMR. We report our single-center experience on AAMR treatment. MATERIALS AND METHODS: We treated 23 transplanted patients (group A) with protein-A immunoadsorption (IA) and 7 patients (group B) with double-filtration plasmapheresis. All patients were treated with IVIG (400 mg/kg/d). Basic immunosuppression included cyclosporine, steroids, azathioprine, and antilymphocyte globulin or monoclonal antibodies (OKT3). A subgroup of 3 patients (3/7; group B1) was treated with photopheresis. RESULTS: In both groups, the mean number of extracorporeal procedures was 7.3 ± 4.5 and 5.5, respectively; the mean duration of treatment was 12.3 ± 10.2 and 14.5 days, respectively. In group A, we observed negative cross-matching in 96% after mean of 18 days; 1 patient died from sepsis, and 6 lost their grafts. In group B, negative circulating DSA were observed in all patients after a mean of 25 days, and 1 patient lost their allograft. CONCLUSIONS: In our observation, the 2 extracorporeal procedures had similar effects in terms of graft survival, DSA removal, and cross-match negativity (group A 74% vs 86%; 95.6% vs 100%). IA was faster for DSA removal. In our opinion, the higher costs of IA suggests its use just in high-risk cases, such as in hyperimmune or sensitized patients. Further studies are necessary to improve our knowledge.

Diaphragmatic hernia as a spontaneous sequela of a surgically-treated left infiltrating renal tumor: a case report.

A diaphragmatic hernia is a protrusion of abdominal structures within the thoracic cavity through a defect in the diaphragm, which can be either congenital or acquired. Diaphragmatic rupture, as a sequela following abdominal surgery, is rarely documented. Approximately 80% of the reported cases, the injury occurred on the left side. We discuss a case of a 37 year-old male who underwent a left nephrectomy with ipsilateral adrenalectomy and diaphragmatic resection, by direct reconstruction that developed the sequela of a diaphragmatic hernia. We chose a surgical transthoracic approach for herniation repair.

From listing to transplant: nephrologic monitoring in cirrhotic patients awaiting liver transplantation.

Nephrologic monitoring of end-stage liver disease (ESLD) patients is part of evaluation for orthotopic liver transplantation (OLT). The numerous causes of renal dysfunction in ESLD patients sometimes relate to the extent of liver damage or sometimes more closely to organic nephropathy. The aim of this study was to evaluate renal function through a specific nephrologic form applied in our outpatient clinic to optimize nephrologic monitoring in ESLD patients awaiting OLT. We enrolled 69 cirrhotic patients (56 men, 13 women) awaiting OLT from April 2008 to January 2012. All patients were evaluated at listing and every 3 months until OLT. The most interesting result was the stable values of serum creatinine from listing to transplantation. We think that dedicated liver transplant nephrologic evaluation is important in the follow-up of ESLD patients awaiting OLT, because the presence of renal dysfunction may represent an important criterion for specific therapeutic interventions to minimize pre-OLT renal injuries that limit the effect of impaired renal function on patient outcomes.