Venkatesh K. Ariyamuthu

Bath salt intoxication causing acute kidney injury requiring hemodialysis

Traditional bath salts contain a combination of inorganic salts like Epsom salts, table salt, baking soda, sodium metaphosphate, and borax that have cleansing properties. Since 2010, there have been rising concerns about a new type of substance abuse in the name of “bath salts.” They are beta‐ketone amphetamine analogs and are derivates of cathinone, a naturally occurring amphetamine analog found in the “khat” plant (Catha edulis). Effects reported with intake included increased energy, empathy, openness, and increased libido. Serious adverse effects reported with intoxication included cardiac, psychiatric, and neurological signs and symptoms. Not much is known about the toxicology and metabolism of these compounds. They inhibit monoamine reuptake (dopamine, nor epinephrine, etc.) and act as central nervous system stimulants with high additive and abuse potential because of their clinical and biochemical similarities to effects from use of cocaine, amphetamine, and 3,4‐methylenedioxy‐N‐methylamphetamine. Deaths associated with use of these compounds have also been reported. We report a case of acute kidney injury associated with the use of “bath salt” pills that improved with hemodialysis.

Cellular and molecular immune profiles in renal transplant recipients after conversion from tacrolimus to sirolimus

Tacrolimus and Sirolimus are commonly used maintenance immunesuppressants in kidney transplantation. Since their effects on immune cells and allograft molecular profiles have not been elucidated, we characterized the effects of Tacrolimus to Sirolimus conversion on frequency and function of T cells, and on graft molecular profiles. Samples from renal transplant patients in a randomized trial of 18 patients with late Sirolimus conversion and 12 on Tacrolimus maintenance were utilized. Peripheral blood was collected at 0, 6, 12 and 24-months post-randomization with T cell subpopulations analyzed by flow cytometry and T cell alloreactivity tested by IFN-γ ELISPOT. Graft biopsy samples obtained 24-months post-randomization were used for gene expression analysis. Sirolimus conversion led to an increase in CD4+25+++Foxp3+ regulatory T cells. While Tacrolimus-maintained patients showed a decrease in indirect alloreactivity over time post-transplant, Sirolimus conversion increased indirect alloreactive T cell frequencies compared to Tacrolimus-maintained patients. No histological differences were found in graft biopsies, but molecular profiles showed activation of the antigen presentation, IL-12 signaling, oxidative stress, macrophage-derived production pathways, and increased inflammatory and immune response in Sirolimus-converted patients. Thus, chronic immune alterations are induced after Sirolimus conversion. Despite the molecular profile being favorable to calcineurin inhibitor-based regimen, there was no impact in renal function over 30 months of follow-up.

Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate

BACKGROUND AND OBJECTIVES IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents. We initially divided the cohort into two groups on the basis of steroid use at the time of discharge: steroid (n=59,010) versus no steroid (n=15,617). Each group was stratified into induction categories: IL2-RA, rabbit antithymocyte globulin (r-ATG), alemtuzumab, and no induction. The main outcomes were incidence of acute rejection within the first year and overall graft failure (defined as graft failure and/or death) post-transplantation. Propensity score (PS), specifically inverse probability of treatment weight, analysis was used to minimize selection bias caused by nonrandom assignment of induction therapies. RESULTS Median (25th, 75th percentiles) follow-up times were 3.9 (1.1, 5.9) and 3.2 (1.1, 4.9) years for steroid and no steroid groups, respectively. Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category (13.3%; P<0.001 and 28%; P=0.01, respectively) in the steroid group and the IL2-RA category (11.1%; P=0.16 and 27.4%; P<0.001, respectively) in the no steroid group. Compared with IL2-RA, PS-weighted and covariate-adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories, except that acute rejection was significantly lower with r-ATG (odds ratio [OR], 0.68; 95% confidence interval [95% CI], 0.62 to 0.74). In the no steroid group, compared with IL2-RA, odds of acute rejection with r-ATG (OR, 0.80; 95% CI, 0.60 to 1.00) and alemtuzumab (OR, 0.68; 95% CI, 0.53 to 0.88) were lower, and r-ATG was associated with better graft survival (hazard ratio, 0.86; 95% CI, 0.75 to 0.99). CONCLUSIONS In DDRT, compared with IL2-RA induction, no induction was associated with similar outcomes when TAC/MPA/steroids were used. r-ATG seems to offer better graft survival over IL2-RA in steroid avoidance protocols.

Periodontal disease in chronic kidney disease and end-stage renal disease patients: a review.

Periodontal disease is a chronic inflammatory disorder and being so it has been associated with accelerated atherosclerosis and malnutrition. Cardiovascular diseases are the leading cause of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients [National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases: Annual Data Report, 2010]. A recent scientific statement released by the American Heart Association [Lockhart et al.: Circulation 2012;125:2520-2544] claims that, even though evidence exists to believe that periodontal interventions result in a reduction in systemic inflammation and endothelial dysfunction, there is little evidence that those interventions prevent atherosclerotic vascular disease or modify the outcomes. In this review, we discuss the periodontal findings and their association with an increased prevalence of inflammatory markers and cardiovascular mortality in ESRD patients and CKD.

Decompensated high-output congestive heart failure in a patient with AVF and the role of right heart catheterization: a case study.

A 70‐year‐old Caucasian male presented 8 months postcadaveric renal transplant with slowly progressive shortness of breath, abdominal distention, and cough for a duration of a few days. Thorough evaluation found him to have severe pulmonary hypertension (PH) on echocardiogram with decompensated high‐output congestive heart failure. A right heart catheterization was done, which confirmed elevated right‐sided pressures and high cardiac output. The mean pulmonary artery pressure, on a Swan–Ganz catheter, improved from 37 to 30 mmHg on partial manual occlusion of his still functioning hemodialysis arteriovenous fistula. Subsequently, the patient underwent ligation of the fistula and this led to gradual improvement in his symptoms. Follow‐up right heart catheterization and echocardiogram showed marked improvement and normalization of right heart pressures. We recommend that patients with arteriovenous fistula should undergo close monitoring for development of early signs and symptoms of congestive heart failure and screening for PH by echocardiography post‐kidney transplant. Right heart catheterization should be considered if screening is positive. Risk and benefit of fistula closure should be weighed in face of reduced survival from PH in dialysis patients and closure should be considered in post‐transplant patients.

Images in clinical medicine. Chvostek's sign and carpopedal spasm.

A 35-year-old man presented with a 2-day history of cramps and paresthesias in the arms, predominantly involving the fingers. He had carpopedal spasm, which was reproducible by inflating a blood-pressure cuff on his arm, and Chvosteks sign.

Kidney Diseases Associated With Alternative Complement Pathway Dysregulation and Potential Treatment Options

&NA; Atypical hemolytic uremic syndrome and C3 glomerulopathy (dense deposit disease and C3 glomerulonephritis) are characterized as inappropriate activation of the alternative complement pathway. Genetic mutations affecting the alternative complement pathway regulating proteins (complement factor H, I, membrane cofactor protein and complement factor H–related proteins) and triggers (such as infection, surgery, pregnancy and autoimmune disease flares) result in the clinical manifestation of these diseases. A decade ago, prognosis of these disease states was quite poor, with most patients developing end‐stage renal disease. Furthermore, renal transplantation in these conditions was associated with poor outcomes due to graft loss to recurrent disease. Recent advances in targeted complement inhibitor therapy resulted in significant improvement in disease remission, renal recovery, health‐related quality of life and allograft survival.

Isolated pleural effusion as a presentation of high cardiac output heart failure in a hemodialysis patient.

Congestive heart failure is a well‐recognized complication of hemodialysis arteriovenous fistula. Symptoms of dyspnea are usually associated with signs of congestive heart failure including pulmonary edema, pleural effusions, lower extremity edema, and liver enlargement, to name a few. We present a case of a gentleman with end‐stage renal disease on chronic hemodialysis, which developed acute bilateral transudative pleural effusions in the absence of other signs of systemic venous congestion, associated with pulmonary venous congestion. We also discuss the pathogenesis and role of hemodialysis in management of this patient.

Induction regimen and survival in simultaneous heart-kidney transplant recipients

BACKGROUND Induction therapy in simultaneous heart-kidney transplantation (SHKT) is not well studied in the setting of contemporary maintenance immunosuppression consisting of tacrolimus (TAC), mycophenolic acid (MPA), and prednisone (PRED). METHODS We analyzed the Organ Procurement and Transplant Network registry from January 1, 2000, to March 3, 2015, for recipients of SHKT (N = 623) maintained on TAC/MPA/PRED at hospital discharge. The study cohort was further stratified into 3 groups by induction choice: induction (n = 232), rabbit anti-thymoglobulin (r-ATG; n = 204), and interleukin-2 receptor-α (n = 187) antagonists. Survival rates were estimated using the Kaplan-Meier estimator. Multivariable inverse probability weighted Cox proportional hazard regression models were used to assess hazard ratios associated with post-transplant mortality as the primary outcome. The study cohort was censored on March 4, 2016, to allow at least 1-year of follow-up. RESULTS During the study period, the number of SHKTs increased nearly 5-fold. The Kaplan-Meier survival curve showed superior outcomes with r-ATG compared with no induction or interleukin-2 receptor-α induction. Compared with the no-induction group, an inverse probability weighted Cox proportional hazard model showed no independent association of induction therapy with the primary outcome. In sub-group analysis, r-ATG appeared to lower mortality in sensitized patients with panel reactive antibody of 10% or higher (hazard ratio, 0.19; 95% confidence interval, 0.05-0.71). CONCLUSION r-ATG may provide a survival benefit in SHKT, especially in sensitized patients maintained on TAC/MPA/PRED at hospital discharge.

Pathogenesis and Management of Dialysis Access Infections

Infections related to dialysis access devices are a common cause of morbidity and mortality in dialysis dependent end-stage renal disease patients. Catheter related blood stream infections and their related complications in hemodialysis, and peritonitis in peritoneal dialysis are a significant threat to the continued use of the respective dialysis access devices. They lead to interruption of regular dialysis, increased hospitalization rates and health care costs for their management. The incidence of infectious complications can be decreased as the factors that confer an increased risk of such access device infections are potentially modifiable. This chapter discusses the epidemiology, pathogenesis, risk factors, clinical manifestations, treatment and prevention of both hemodialysis and peritoneal dialysis access device related infectious complications.