Negiin Pourafshar

Uric acid and the prediction models of tumor lysis syndrome in AML.

We investigated the ability of serum uric acid (SUA) to predict laboratory tumor lysis syndrome (LTLS) and compared it to common laboratory variables, cytogenetic profiles, tumor markers and prediction models in acute myeloid leukemia patients. In this retrospective study patients were risk-stratified for LTLS based on SUA cut-off values and the discrimination ability was compared to current prediction models. The incidences of LTLS were 17.8%, 21% and 62.5% in the low, intermediate and high-risk groups, respectively. SUA was an independent predictor of LTLS (adjusted OR 1.12, CI95% 1.0–1.3, p = 0.048). The discriminatory ability of SUA, per ROC curves, to predict LTLS was superior to LDH, cytogenetic profile, tumor markers and the combined model but not to WBC (AUCWBC 0.679). However, in comparisons between high-risk SUA and high-risk WBC, SUA had superior discriminatory capability than WBC (AUCSUA 0.664 vs. AUCWBC 0.520; p <0.001). SUA also demonstrated better performance than the prediction models (high-risk SUAAUC 0.695, p<0.001). In direct comparison of high-risk groups, SUA again demonstrated superior performance than the prediction models (high-risk SUAAUC 0.668, p = 0.001) in predicting LTLS, approaching that of the combined model (AUC 0.685, p<0.001). In conclusion, SUA alone is comparable and highly predictive for LTLS than other prediction models.

Urine Ammonium, Metabolic Acidosis and Progression of Chronic Kidney Disease

The metabolism of a typical Western diet generates 50–100 mEq of acid (H+) per day, which must be excreted in the urine for the systemic acid-base to remain in balance. The 2 major mechanisms that are responsible for the renal elimination of daily acid under normal conditions are ammonium (NH4+) excretion and titratable acidity. In the presence of systemic acidosis, ammonium excretion is intensified and becomes the crucial mechanism for the elimination of acid. The impairment in NH4+ excretion is therefore associated with reduced acid excretion, which causes excess accumulation of acid in the body and consequently results in metabolic acidosis. Chronic kidney disease (CKD) is associated with the impairment in acid excretion and precipitation of metabolic acidosis, which has an adverse effect on the progression of CKD. Recent studies suggest that the progressive decline in renal ammonium excretion in CKD is an important determinant of the ensuing systemic metabolic acidosis and is an independent factor for predicting the worsening of kidney function. While these studies have been primarily performed in hypertensive individuals with CKD, a closer look at renal NH4+ excretion in non-hypertensive individuals with CKD is warranted to ascertain its role in the progression of kidney disease.

The utility of trough mycophenolic acid levels for the management of lupus nephritis

Background Monitoring of mycophenolic acid (MPA) levels may be useful for effective mycophenolate mofetil (MMF) dosing. However, whether commonly obtained trough levels are an acceptable method of surveillance remains debatable. We hypothesized that trough levels of MPA would be a poor predictor of area under the curve (AUC) for MPA. Methods A total of 51 patients with lupus nephritis who were on MMF 1500 mg twice a day and had a 4-h AUC done were included in this study. MPA levels were measured prior to (C0) and at 1 (C1), 2 (C2) and 4 (C4) h, followed by 1500 mg of MMF. The MPA AUC values were calculated using the linear trapezoidal rule. Regression analysis was used to examine the relationship between the MPA trough and AUC. Differences in the MPA trough and AUC between different clinical and demographic categories were compared using t-tests. Results When grouped by tertiles there was significant overlap in MPA, AUC 0-4 and MPA trough in all tertiles. Although there was a statistically significant correlation between MPA trough levels and AUC, this association was weak and accounted for only 30% of the variability in MPA trough levels. This relationship might be even more unreliable in men than women. The use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with increased MPA trough levels and AUC at 0-4 h (AUC0-4). Conclusion Trough levels of MPA do not show a strong correlation with AUC. In clinical situations where MPA levels are essential to guide therapy, an AUC0-4 would be a better indicator of the adequacy of treatment.

Thiazide Therapy in Chronic Kidney Disease: Renal and Extra Renal Targets.

BACKGROUND Thiazides are the most commonly used medications for the treatment of mild and moderate hypertension. Despite their recognized effect, the mechanism by which thiazides reduce systemic blood pressure remains uncertain. The prevailing belief is that thiazides reduce blood pressure primarily via enhancement of salt excretion consequent to the inhibition of the Na-Cl Cotransporter (NCC) in the Distal Convoluted Tubules (DCT). However, recent reports point to a reduction in peripheral vascular resistance as a major mechanism of antihypertensive effect of thiazides. It is plausible that both mechanisms, renal and extra-renal, may be operating simultaneously. Recent studies point to compensatory mechanisms in the kidney distal nephron that may play a role in blunting the diuretic effect of thiazides. Not much information is available about the efficacy of thiazides in controlling blood pressure in individuals with Chronic Kidney Disease (CKD). OBJECTIVE This review will discuss the latest updates on the use and efficacy of thiazides derivatives as diuretics and antihypertensive medications in CKD patients. CONCLUSION Thiazides remain effective as diuretics and antihypertensive agents in individuals with low GFR.

Pulmonary and tricuspid valvuloplasty in carcinoid heart disease

A 26‐year‐old female with carcinoid heart disease consisting of severe pulmonary and tricuspid valve stenosis was admitted with line associated sepsis. She recovered from sepsis with antibiotics and aggressive fluid resuscitation but became grossly volume overloaded with evidence of tense ascites and lower extremity edema. She developed worsening renal and hepatic function due to congestive nephropathy and hepatopathy, which did not respond to intravenous diuretics, and she was deemed too sick for surgical pulmonary and tricuspid valve replacement. Pulmonary and tricuspid valvuloplasty was performed as a rescue measure to alleviate her congestive symptoms and improve her candidacy for valve replacement.

Babesiosis: An unusual cause of sepsis after kidney transplantation and review of the literature

We report a unique case of babesiosis presenting as sepsis after kidney transplantation. A 70‐year‐old female kidney transplant recipient presented with fever, hemolytic anemia, and acute kidney injury, and met three of four systemic inflammatory response syndrome criteria. Serology was positive for Babesia microti, confirmed by polymerase chain reaction. The patient was treated with atovaquone and azithromycin and made a full recovery. Reports of babesiosis after solid organ transplantation are rare, with only four prior cases reported in the literature. We report the first case of babesiosis, to our knowledge, presenting as sepsis that was successfully treated after solid organ transplantation.

Need for Raising Awareness - Monitoring Urinary Protein Excretion in Cardiac Transplant Patients Receiving Mammalian Target of Rapamycin Inhibitors

version from a CNI-based regimen, were included. The clinical and laboratory records were reviewed and monitoring trends of urinary protein excretion through qualitative (urine analysis) or quantitative measurements were explored before and after the initiation of mTORi. Out of 411 OHT patients who were included, 91 (22%) received an mTORi (72 sirolimus and 19 everolimus), which was started de novo in 32 out of 91 (35%) of patients. Prior to the initiation of mTORi, urine protein excretion had been assessed only in 56 out of 91 (62%) patients with either urinalysis (26/91 (29%)) or quantitatively (30/91 (33%)). After the initiation of mTORi therapy, only 60 out of 91 (66%) patients had at least onetime evaluation for proteinuria during follow-up by urine analysis (26/91; 29%) or quantitatively (34/91; 37%). The timing of the measurement of proteinuria was highly variable ranging from 4 weeks to 7 years after starting mTORi (median 15.7 months). Among patients who received mTORi, 31 (34%) patients had no assessment of proteinuria throughout their transplant follow-up. These results reveal that a significant subset of OHT recipients (i.e. more than a third) may not undergo any assessment of urinary protein excretion prior to Dear editor, Proteinuria is a well-recognized complication of the mammalian target of rapamycin inhibitors (mTORi) in renal transplant recipients and is associated with an adverse impact on the outcomes [1, 2] . These macrolide antibiotics with potent antiproliferative and antirejection properties are also used in the setting of orthotopic heart transplantation (OHT) in an attempt to avoid the nephrotoxicity of calcineurin inhibitors (CNIs) or to slow the progression of cardiac allograft vasculopathy. Although renal complications of mTORi are not as widely studied in OHT, emerging evidence suggests that these patients are at higher risk for the development of proteinuria and deterioration in renal function [3, 4] . It has been proposed that OHT patients receiving mTORi should be monitored for the development of proteinuria, as early detection and management of this complication could conceivably result in improved renal outcomes [3] . We studied the monitoring trends of OHT recipients in our institution with respect to the development of proteinuria in those who received an mTORi-based regimen. All patients who underwent OHT between January 2000 and December 2015 and received an mTORi, whether de novo or following conReceived: August 26, 2016 Accepted after revision: September 30, 2016 Published online: November 8, 2016

High-risk Trans-Catheter Aortic Valve Replacement in a Failed Freestyle Valve with Low Coronary Height: A Case Report

A 55-year-old male with a history of two prior cardiac surgeries presented with decompensated heart failure due to severe bioprosthetic aortic valve insufficiency. A third operation was viewed prohibitively high risk and valve-in-valve trans-catheter aortic valve replacement was considered. There were however several high-risk features and technically challenging aspects including low coronary ostia height, poor visualization of the aortic sinuses, and difficulty in identification of the coplanar view due to severe aortic insufficiency, and a highly mobile aortic valve mass. After meticulous peri-procedural planning, trans-catheter aortic valve replacement was carried out with a SAPIEN 3 balloon-expandable valve without any complication. Strategies undertaken to navigate the technically challenging aspects of the case are discussed.