Absence of hemoglobin increase is associated with reduced graft survival after kidney transplantation.

BACKGROUND: Anemia is prevalent following kidney transplantation and is associated with reduced graft survival. The association between temporal changes in hemoglobin (Hb) level at the early post-transplant period and graft survival is unknown. PATIENTS AND METHODS: The study cohort included consecutive patients included in a single center transplantation registry between January 2002 and December 2016. Temporal changes in Hb values during the first 90 days after the transplantation were evaluated by piecewise linear regression model. Significant Hb increase rate was defined as an increase of .5 gram/deciliter/month. Patients were divided into groups according to the presence of significant Hb increase. The primary outcome was death-censored graft failure. RESULTS: Of 946 patients included in the study cohort, 831 (87.8%) had at least one interval of Hb increase, and 115 (12.2%) had no Hb increase. The absence of Hb increase was associated with an elevated risk of death censored graft failure by univariate (HR 2.9, 95% CI 1.88-4.49, P < .001) and multivariate (HR 2.47, 95% CI 1.48-4.12, P = .001) analyses. The timing and rate of Hb increase had no association with the main outcome. CONCLUSIONS: Lack of Hb increase during the early post-transplant period is associated with an increased risk of graft loss.

Post-transplantation erythrocytosis in kidney transplant recipients-A retrospective cohort study.

OBJECTIVES: To characterize risk factors for the development of post-transplant erythrocytosis (PTE), and its long-term effect on mortality, graft failure, and thrombosis. METHODS: Retrospective study including all kidney transplant recipients in Rabin Medical Center (RMC) during the years 2005-2014. The primary outcome was a composite outcome of all-cause mortality or graft failure at the end of follow-up. Secondary outcomes included death censored graft loss, venous thromboembolism, major adverse cardiovascular events, and mortality. A matched control group was also evaluated. Univariate and multivariate time-varying Cox model analyses were conducted for outcome evaluation. RESULTS: A total of 1304 patients were included, 169 of whom were diagnosed with PTE (12.9%). PTE was associated with male gender, higher glomerular filtration rate (GFR), and polycystic kidney disease. PTE was found to be associated with a reduced risk of the primary outcome (HR 0.355, CI 95% 0.151-0.89, P = .027) in a univariate time-varying Cox analysis, but was not associated with the composite outcome in a multivariate analysis. There was no difference in the primary outcome when the PTE group was compared with the matched control. CONCLUSION: PTE was not found to be associated with long-term outcomes of graft failure and poor survival.

Iron Deficiency Anemia in Chronic Kidney Disease.

Iron deficiency anemia is a common complication of chronic kidney disease (CKD). CKD patients suffer from both absolute and functional iron deficiency. Absolute iron deficiency is defined by severely reduced or absent iron stores, while functional iron deficiency is defined by adequate iron stores but insufficient iron availability for incorporation into erythroid precursors. This is due to increased levels of hepcidin. Anemia in CKD is associated with an increased risk of morbidity and mortality. The association between anemia and mortality may be related to the severity of anemia. All CKD patients should be screened for anemia during the initial evaluation for CKD. Criteria used to define iron deficiency are different among CKD compared to normal renal function. Among CKD patients, absolute iron deficiency is defined when the transferrin saturation (TSAT) is ≤20% and the serum ferritin concentration is ≤100 ng/mL among predialysis and peritoneal dialysis patients or ≤200 ng/mL among hemodialysis patients. Functional iron deficiency, also known as iron-restricted erythropoiesis, is characterized by TSAT ≤20% and elevated ferritin levels. Iron supplementation is recommended for all CKD patients with anemia. There is general agreement according to guidelines that intravenous (i.v.) iron supplementation is the preferred method for CKD patients on dialysis (CKD stage 5D) and either i.v. or oral iron is recommended for patients with CKD ND (CKD stages 3-5). In this review we discuss the evidence base for these recommendations.

Post renal transplant anemia: severity, causes and their association with graft and patient survival.

BACKGROUND: Post transplantation anemia (PTA) is common among kidney transplant patients. PTA is associated with increased graft loss and in most studies with increased mortality. However, the effect of the severity of anemia on this associations was not thoroughly evaluated. METHODS: Patients who underwent kidney transplantation in Rabin Medical Center (RMC) were included in the study. Data were collected during the years 2002-2016. Anemia was defined as hemoglobin (Hb) level less than 12 g/dL in women and less than 13 g/dL in men, in accordance with World Health Organization (WHO) criteria. Severe anemia was defined as hemoglobin lower than 11 g/dL. Primary outcome was a composite of patient and graft survival. We used univariate and multivariate models to evaluate association between severity and specific causes of anemia with the outcomes. As the risk associated with anemia changed over time we analyzed the risk separately for the early and the late period (before and after 1251 days). RESULTS: Our cohort included 1139 patients, 412 (36.2%) of which had PTA and 134 (11.7%) had severe anemia. On multivariable analysis, severe anemia was highly associated with the primary outcome at the early period (HR 6.26, 95% CI 3.74-10.5, p < 0.001). Anemia due to either AKI & acute rejection (11.9% of patients) or infection (16.7%), were associated with primary outcome at the early period (HR 9.32, 95% CI 5.3-26.41, p < 0.001 and HR 3.99, 95% CI 2.01-7.95, p < 0.001, respectively). There was non-significant trend for association between anemia due to Nutritional deficiencies (29.1%) and this outcome (HR 3.07, 95% CI 0.93-10.17, p = 0.067). CONCLUSION: PTA is associated with graft loss and mortality especially during the first three years. Anemia severity affects this association. An anemia workup is recommended for PTA.

Medication-induced SIADH: distribution and characterization according to medication class.

AIMS: The aims of the current study were to determine the distribution of aetiologies for the drug-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) in hospitalized patients, and to characterize them according to the different drug groups. METHODS: A single-centre retrospective study was carried out, including all patients diagnosed with SIADH in a large community hospital and tertiary centre between 1 January 2007 and 1 January 2013 who were treated with drugs known to be associated with SIADH. Two physicians reviewed every patient's medical file for predetermined relevant clinical data. RESULTS: The study cohort included 198 patients who had SIADH and received drugs associated with SIADH. Most patients [146 (73.7%)] were diagnosed with drug-associated SIADH, while 52 (26.3%) were diagnosed with SIADH due to other aetiologies. The Naranjo algorithm differentiated well between the two groups (P < 0.001). Five drug classes (antidepressants, anticonvulsants, antipsychotic agents, cytotoxic agents and pain medications) were implicated in 82.3% of patients diagnosed with drug-associated SIADH. Specific serotonin reuptake inhibitors and carbamazepine were commonly implicated. There were no clinically significant differences in the characteristics or severity of SIADH according to drug class. CONCLUSIONS: The clinical characteristics of SIADH caused by different drugs are comparable. Patients with SIADH treated with drugs from five common medication classes will probably be diagnosed with drug-induced SIADH. Physicians should be aware of the significance of these medication classes as SIADH aetiologies.

Early endoscopic, laboratory and clinical predictors of poor disease course in paediatric ulcerative colitis.

OBJECTIVE: Data to support treatment algorithms in ambulatory paediatric UC are scarce. We aimed to explore the 1 year outcome in an inception cohort of paediatric UC patients and to identify early predictors of good outcome that might serve as short term treatment targets. DESIGN: A chart review of 115 children with new onset UC was performed (age 11 ± 4.1 years; 58 (50%) males; 86 (75%) extensive colitis; 70 (61%) moderate-severe disease; 63 (55%) received steroids at baseline). We assessed the Paediatric Ulcerative Colitis Activity Index (PUCAI) and laboratory variables at the time of diagnosis and at 3 months, and endoscopy at diagnosis. RESULTS: The 3 month PUCAI was the strongest predictor of 1 year sustained steroid free remission (SSFR) (area under the receiver operating characteristic curve (AUROC)=0.7 (95% CI 0.6 to 0.8) and colectomy by 2 years (AUROC=0.75 (0.6 to 0.89)). SSFR was achieved in 9/54 (17%) children who had active disease (PUCAI ≥ 10) at 3 months (negative predictive value (NPV)=83%) and by 4/46 (8.6%) of those with a PUCAI score >10; (NPV=91%, positive predictive value=52%; p<0.001), implying that PUCAI >10 at 3 months has a probability of 9% for achieving SSFR versus 48% with a PUCAI value of ≤10. None of the variables at baseline was predictive of SSFR or colectomy (endoscopic severity, disease extent, age, PUCAI or C reactive protein/erythrocyte sedimentation rate/albumin/haemoglobin; all AUROC<0.6, p>0.05) but baseline PUCAI predicted subsequent acute severe colitis and the need for salvage medical therapy. CONCLUSIONS: Completeness of the early response appears more important than baseline UC severity for predicting outcome in children, and supports using PUCAI<10 as a feasible treatment goal. Our data suggest that treatment escalation should be considered with a PUCAI value of ≥ 10 at 3 months.

Plasma porphyrins among end stage renal disease patients and cutaneous symptoms- is there still an association?

Introduction: Several abnormalities of porphyrin metabolism leading to Porphyria Cutanea Tarda (PCT) have been described in early studies of End Stage Renal Disease (ESRD) patients, with a reported prevalence of 5-18%. We aimed to evaluate porphyrin levels and correlation to skin manifestations in modern dialysis era. Methods: The study cohort included adult hemodialysis patients from a single center tertiary medical center. All patients underwent a full skin examination, completed the Dermatology Life Quality Index questioner, and provided a blood sample for porphyrin levels assessment. Results: A total of 94 adult hemodialysis patients were recruited to the study. No clinical PCT was diagnosed. Porphyrin levels did not correlate with any clinical or dialysis quality parameters. Conclusions: In modern hemodialysis era, possibly due to improved porphyrins' metabolism and dialysis removal, PCT is much less prevalent among hemodialysis patients than previously reported in the past.

Glycemic patterns detected by continuous subcutaneous glucose sensing in children and adolescents with type 1 diabetes mellitus treated by multiple daily injections vs continuous subcutaneous insulin infusion.

OBJECTIVE: To compare glycemic patterns by mode of therapy in children with type 1 diabetes mellitus using the Continuous Glucose Monitoring System (CGMS). DESIGN: Open randomized crossover comparing 3(1/2) months of multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII). SETTING: Tertiary care, university-affiliated medical center. Patients Twenty-three children and adolescents with type 1 diabetes mellitus. INTERVENTIONS: The CGMS was applied for 72 hours after 1 month and at the end of each study arm. MAIN OUTCOME MEASURES: Hemoglobin A(1c) levels and glucose level profiles were compared between the 2 study arms and the 2 sensor applications for each arm. RESULTS: The arms were similar for mean (SD) hemoglobin A(1c) levels (CSII, 8.0% [0.8%]; and MDI, 8.2% [0.8%]) and glucose levels. Areas under the curve were significantly larger during MDI for nocturnal and 24-hour hypoglycemia (P =.01 and.04, respectively) and for postprandial hypoglycemia and hyperglycemia (P =.03 and.05, respectively). The rate of hyperglycemia increased during CSII (P =.03), but 24-hour duration and area under the curve for hyperglycemia were similar. Compared with the first CGMS reading in each arm, the second had a longer mean duration of postprandial within-target glucose levels (P =.04), tendency for lower rate of diurnal hypoglycemic events (P =.1), shorter duration of nocturnal hypoglycemia (P =.05), and smaller 24-hour area under the curve for hypoglycemia (P =.04). CONCLUSIONS: Intensive treatment with CSII seemed to be associated with slightly better prebreakfast, postprandial, and within-target glucose profiles than MDI, as well as a smaller area under the curve for hypoglycemia. Lower hypoglycemia-related variables in the second sensor reading in each arm indicate that the CGMS may serve as an educational tool to decrease the rate and magnitude of hypoglycemia.

A prototype of a new noninvasive device to detect nocturnal hypoglycemia in adolescents with type 1 diabetes--a pilot study.

BACKGROUND: Severe hypoglycemic events are a major consequence of tight diabetes control. Continuous glucose monitoring systems (CGMSs) were recently introduced in order to minimize the risk of hypoglycemia. However, the present CGMSs are invasive and costly and have been recently demonstrated to be intolerant for most children and adolescents. Hence there is a need for a simple, noninvasive, convenient, and inexpensive device to detect hypoglycemic events. The Gili Medical Hypoglycemia Non Invasive Monitoring System (GMHNIMS) (Gili Medical Ltd., Migdal HaEmek, Israel) has been currently developed for these purposes. SUBJECTS AND METHODS: Ten patients 14-18 years old with type 1 diabetes for at least 1 year participated in a pilot study that was held at the Meyer Children's Hospital, Rambam Medical Center, Haifa, Israel. All patients were either treated by insulin pump or by multiple daily injections. The GMHNIMS was connected to the study subjects during three consecutive nights in an inpatient setting while they received their usual insulin regimen. The system is composed of four sensors (heart rate, perspiration, skin temperature, and tremor) that detect physiologic changes during hypoglycemia. In addition, each patient was connected to a real-time CGMS for 3 nights. When a hypoglycemic event was suspected clinically by the patient, a bedside capillary glucose was checked by a glucometer. RESULTS: The system was found to be convenient without any disturbances to sleep quality. The sensitivity of the GMHNIMS for detection of true hypoglycemic events was 100% with specificity of 85.7%. CONCLUSIONS: The new device showed high detection rates of nocturnal hypoglycemic events with an acceptable degree of false-positive readings. Being inexpensive and noninvasive, this device has the potential for routine use in insulin-treated patients.