Zeenat Yousuf Bhat

Understanding the Risk Factors and Long-Term Consequences of Cisplatin-Associated Acute Kidney Injury: An Observational Cohort Study

Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk factors for development of cisplatin-associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99±9mg/m2) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI<60mL/min/1.73m2. The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p<0.05). African American race was a significant risk factor for cisplatin-associated AKI, OR 2.8 (95% CI 1.3 to 6.3) and 2.8 (95% CI 1.2 to 6.7) patients with stage III AKI had the lowest eGFR value at 12 months (p = 0.05) and long-term patient survival (HR 2.1; p<0.01) than patients with no or lower grades of AKI. Most common causes of death were recurrent cancer (44%) or secondary malignancy elsewhere (40%). Cisplatin-associated severe AKI occurs in 20% of the patients and has a negative impact on long-term renal function and patient survival. PEG tube placement may be protective and should be considered in high risk-patients.

Growth Differentiation Factor-15 and Risk of CKD Progression

Growth differentiation factor-15 (GDF-15) is a member of the TGF-β cytokine superfamily that is widely expressed and may be induced in response to tissue injury. Elevations in GDF-15 may identify a novel pathway involved in loss of kidney function among patients with CKD. Among participants in the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS), we tested whether kidney tissue expression of GDF15 mRNA correlates with circulating levels of GDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function. In matching samples of 24 patients with CKD from the C-PROBE study, circulating GDF-15 levels significantly correlated with intrarenal GDF15 transcript levels (r=0.54, P=0.01). Among the 224 C-PROBE and 297 SKS participants, 72 (32.1%) and 94 (32.0%) patients, respectively, reached a composite end point of 30% decline in eGFR or progression to ESRD over a median of 1.8 and 2.0 years of follow up, respectively. In multivariable models, after adjusting for potential confounders, every doubling of GDF-15 level associated with a 72% higher (95% confidence interval, 1.21 to 4.45; P=0.003) and 65% higher (95% confidence interval, 1.08 to 2.50; P=0.02) risk of progression of kidney disease in C-PROBE and SKS participants, respectively. These results show that circulating GDF-15 levels strongly correlated with intrarenal expression of GDF15 and significantly associated with increased risk of CKD progression in two independent cohorts. Circulating GDF-15 may be a marker for intrarenal GDF15-related signaling pathways associated with CKD and CKD progression.

Severe propylene glycol toxicity secondary to use of anti-epileptics.

Propylene glycol toxicity presenting as high anion gap metabolic acidosis and osmolar gap has been extensively reported in literature, and most of them are secondary to intravenous lorazepam infusion. However, propylene glycol is used as a solvent in a number of medications that are frequently utilized in critical care setting, and hence one should be aware that the toxicity is possible from a variety of medication. Phenobarbital and phenytoin are one of those, and we hereby report a novel case of propylene glycol toxicity secondary to phenobarbital and phenytoin infusion in a patient with refractory status epilepticus. Furthermore, our patient had end-stage renal disease, which we think could have been an important precipitating factor for the toxicity. Because most of the symptoms from propylene glycol toxicity can mimic sepsis—which is very common in critical care unit patients—this life threatening scenario could be easily missed. Regular monitoring of osmolar gap is an easily available intervention in the at risk patients.

Immunoglobulin A Nephropathy: A Review of Current Literature on Emerging Pathophysiology

Abstract:Immunoglobulin (Ig) A nephropathy is one of the most common causes of glomerulonephritis worldwide. Its prognosis can be totally different in various patient populations, ranging from asymptomatic slow progression to end-stage renal disease in as much as 40% of patients in few months to years. This disease process can be idiopathic, or it can be associated with a variety of disease processes. Various risk stratification scoring systems are available, which can predict the long-term outcome. New evidences are also emerging that IgA nephropathy is an autoimmune disease with a known antigen, galactose-deficient IgA1, which can elicit an autoantibody response and formation of immune complexes that are deposited in the mesangium.

Impaired β-Oxidation and Altered Complex Lipid Fatty Acid Partitioning with Advancing CKD

Studies of lipids in CKD, including ESRD, have been limited to measures of conventional lipid profiles. We aimed to systematically identify 17 different lipid classes and associate the abundance thereof with alterations in acylcarnitines, a metric of β-oxidation, across stages of CKD. From the Clinical Phenotyping Resource and Biobank Core (CPROBE) cohort of 1235 adults, we selected a panel of 214 participants: 36 with stage 1 or 2 CKD, 99 with stage 3 CKD, 61 with stage 4 CKD, and 18 with stage 5 CKD. Among participants, 110 were men (51.4%), 64 were black (29.9%), and 150 were white (70.1%), and the mean (SD) age was 60 (16) years old. We measured plasma lipids and acylcarnitines using liquid chromatography-mass spectrometry. Overall, we identified 330 different lipids across 17 different classes. Compared with earlier stages, stage 5 CKD associated with a higher abundance of saturated C16-C20 free fatty acids (FFAs) and long polyunsaturated complex lipids. Long-chain-to-intermediate-chain acylcarnitine ratio, a marker of efficiency of β-oxidation, exhibited a graded decrease from stage 2 to 5 CKD (P<0.001). Additionally, multiple linear regression revealed that the long-chain-to-intermediate-chain acylcarnitine ratio inversely associated with polyunsaturated long complex lipid subclasses and the C16-C20 FFAs but directly associated with short complex lipids with fewer double bonds. We conclude that increased abundance of saturated C16-C20 FFAs coupled with impaired β-oxidation of FFAs and inverse partitioning into complex lipids may be mechanisms underpinning lipid metabolism changes that typify advancing CKD.

Colchicine-induced myopathy in a tacrolimus-treated renal transplant recipient: Case report and literature review

Renal transplant recipients are prone to develop drug toxicities because of polypharmacy and drug-drug interactions. Colchicine is often used for the treatment of gout in these patients as nonsteroidal medications are contraindicated. In addition, patients are often on corticosteroids and frequent, periodic, dose escalation for gouty flare may lead to side effects. Colchicine-induced myopathy has been very well described in the literature. Several cases of colchicine toxicity have been reported in cyclosporine-treated patients due to a drug-drug interaction. We report a 62-year-old African American renal transplant recipient who had been doing well on tacrolimus-based immunosuppression and was started on colchicine (0.6 mg twice daily) for gouty flare. A few days later, he was found to have a 4-fold increase in aspartate aminotransferase and an elevated creatine phosphokinase. Although this interaction is very well known with cyclosporine, it has not yet been reported in patients on tacrolimus.

Fibrillary glomerulonephritis in a patient with systemic lupus erythematosus: a rare association

We report the case of a 28-year-old man with systemic lupus erythematosus (SLE) and rapidly progressive glomerulonephritis (RPGN) due to fibrillary glomerulonephritis (FGN). The patient had a history of SLE and had been treated with mycophenolate mofetil, prednisone, and intravenous cyclophosphamide for his renal and extra-renal manifestations. In spite of this treatment, he developed RPGN. A subsequent renal biopsy revealed diffuse proliferative glomerulonephritis with fibrillary deposits. SLE is rarely associated with FGN, however FGN should be considered in the differential diagnosis of any SLE patient with RPGN.

Krokodil-A menace slowly spreading across the Atlantic

Krokodil (also known as crocodile, croc, krok, and poor mans heroin) is a suspension of desomorphine as the core substance with contaminants like iodide, phosphorous, and heavy metals, which are the byproducts of the manufacturing process. The name krokodil emerged due to the appearance of the skin lesions around the injection site, where it turns green and scaly like a crocodile skin due to desquamation. It is also known as the “drug that eats junkies” and “Russias Designer drug.” It is not available as a prescription anywhere in the world. It is a modern day man-made Frankenstein-like drug, which was manufactured due to the pursuit of drug addicts to make a cheap yet effective narcotic but ended up in creating havoc on its users. It has devastating effects on its users, including damage to skin, blood vessels, muscles, bones, and sometimes even multiorgan failure and eventually death. A systemic review was conducted to obtain any available data for the term krokodil to collect information for this article.

A Rare Case of Hyperammonemia Complication of High-Protein Parenteral Nutrition

Hyperammonemia is a metabolic derangement that can be potentially fatal. Primary hyperammonemia due to urea cycle enzyme deficiency is usually discovered in neonates but rarely can present in adulthood. Late-onset manifestations of urea cycle disorders can go unnoticed, until they become life threatening. The authors report a 28-year-old man who developed hyperammonemia in the hospital following parenteral nutrition (PN), leading to cerebral edema, which was fatal despite resolution of the hyperammonemia with cessation of PN and the use of continuous renal replacement therapy.

Tacrolimus toxicity with minimal clinical manifestations: A case report and literature review

Tacrolimus (FK 506 or Fujimycin) is an effective anti–T-cell agent derived from the fungus Streptomyces tsukubaensis. Some in vitro studies have demonstrated that the potency of tacrolimus can be up to 100 times to that of cyclosporine. Despite being a very potent immunosuppressant, its use is complicated by narrow therapeutic range, individual variation in pharmacokinetics, and a broad spectrum of drug interactions. We report a case of very high tacrolimus level (>120 ng/mL) in a patient who was on antiretroviral medication and tacrolimus. Despite having such high drug levels, patients clinical presentation and course was benign. He was managed conservatively and this ordeal resulting in no long-term sequela.