Improvement In Creatinine Research Articles

P0346THE EFFECTS OF RITUXIMAB MAINTENANCE THERAPY ON LUPUS NEPHRITIS

Abstract Background and Aims Lupus Nephritis (LN) is the organ manifestation with the most severe prognosis in Systemic Lupus Erythematosus (SLE). Treatment options are limited due to partial efficacy, intolerance or side effects; moreover 10% of patients reach ESRD despite treatments. Rituximab (RTX) in LN is recommended as second line drug for induction of the remission after failure of Cyclophosphimide or Mycophenolate Mofetil. We have shown a role for RTX as maintenance therapy (RMT) in SLE however the effects of such approach on LN are still unclear. Aim of this study was a sub-analyses of a cohort of SLE patients treated with RTX focusing on the ones with active LN at the moment of the first RTX administration. Methods Patients with active LN at the time of the first RTX administration within a cohort of 147 patients with SLE were identified. Patients with SLE and a flare of LN were classified as treated with a “Single RTX course” (any RTX regimen administered within a single month) (SRC) or with RMT. Patients receiving at least three SRCs with the aim of relapse prevention and within 4 to 8 months between consecutive treatments, were classified as receiving RMT. LN activity was determined according to creatinine, proteinuria and haematuria; complete response (CR) was defined as a decrease of proteinuria to <0.5 g/day, normal creatinine and negative urinary sediment; partial response (PR) was defined as ≥50% improvement in creatinine and proteinuria, treatment failure (TF) was any other condition. A renal flare (RF) was defined as an increase of creatinine and/or proteinuria >30% or the detection of an active urinary sediment due, according to the treating physician, to active disease. Results 33 patients were identified; a renal biopsy had been performed in 76% with prevalence of class IV lupus nephritis in 16/33 (48%). Six months after RTX the rate of CR, PR and TF was respectively 36%, 27% and 36%; proteinuria and the prednisolone dose reduced significantly compared to baseline (respectively from a median of 2200 mg/day (IQR 499-5400) to 850 mg/day (IQR 400-1700) (p=0.005)) and from 25 mg (IQR 11-25) to 10 mg (IQR 6.125-15) (p<0.0001)). At univariate analyses the only factor associate to the risk of TF was a high number of immunosuppressive drugs employed before RTX (p=0.0077). Of the 33 patients, 11 received RMT with a median duration of 18 months (IQR 12,6-23,4) and a median RTX dose of 5 g (IQR 4-6). During the RMT 3 patients experienced a renal flare. The median follow-up after the last RTX administration within the SRC and the RMT groups was respectively 15 months (IQR 13,5-18,4) and 16 months (IQR 3,5-23). Comparing the RF free-survival of the two subgroups after the last RTX infusion, there was a trend towards a longer relapse free survival after the RMT (p=0.057) (figure, left panel). Of interest, the renal relapse free-survival of the 11 patients treated with RMT after the last RTX infusion was significantly longer compared to the one of the same group after the first RTX (p=0.0271) (figure, right panel). The incidence of SAEs per 100 patient years was 0.31 in the SRC group and 0.74 in the RMT group. Conclusion RTX is confirmed as an effective option for patients with LN. A RMT may have a role in improving LN disease control compared to a single RTX administration.

Inhibition of the P2X7 receptor improves renal function via renin-angiotensin system and nitric oxide on diabetic nephropathy in rats

AimTo evaluate the effects of P2X7 receptor blockade on renin-angiotensin system (RAS) in rats with diabetic nephropathy (DN). Main methodsWistar rats were unilaterally nephrectomized and received streptozotocin for diabetes mellitus (DM) induction; control animals (CTL) received the drug vehicle. The animals were submitted to P2X7 receptor silencing, forming the group (DM + siRNA). The animals were placed in metabolic cages for data collection and evaluation of renal function; at the end of the protocol, the kidney was removed for analysis of P2X7, renin, angiotensin-converting enzyme (ACE), ACE2, angiotensin, thiobarbituric acid reactive substance levels (TBARS), nitric oxide (NO) and qualitative histological. Key findingsThe metabolic profile was attenuated in DM + siRNA vs. DM and there was a significant improvement in creatinine, urea and proteinuria levels in the same group. Renin expression was significantly decreased in DM + siRNA vs. DM. ACE and ACE2 were significantly reduced in DM + siRNA vs. DM. TBARS levels were decreased and NO showed an increase in DM + siRNA vs. DM, both significant. All histological alterations were improved in DM + siRNA vs. DM. SignificanceData have shown that although silencing of the P2X7 receptor did not decrease fasting glucose, it promoted an improvement in the metabolic profile and a significant recovery of renal function, revealing a protective action by the inhibition of this receptor. This effect must have occurred due to the inhibition of RAS and the increase of NO, suggesting that the use of P2X7 receptors inhibitors could be used as adjuvant therapy against DN progression.

Chronic treatment of curcumin improves hepatic lipid metabolism and alleviates the renal damage in adenine-induced chronic kidney disease in Sprague-Dawley rats

BackgroundChronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders due to the dysregulation of lipoprotein metabolism which progresses kidney disease. The objective of this study is to evaluate the protective effects of curcumin on dyslipidaemia associated with adenine-induced chronic kidney disease in rats.MethodsMale SD rats (n = 29) were divided into 5 groups for 24 days: normal control (n = 5, normal diet), CKD control (n = 6, 0.75% w/w adenine-supplemented diet), CUR 50 (n = 6, 50 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), CUR 100 (n = 6, 100 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), and CUR 150 (n = 6, 150 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet). The serum and tissue lipid profile, as well as the kidney function test, were measured using commercial diagnostic kits.ResultsThe marked rise in total cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids in serum, as well as hepatic cholesterol, triglyceride and free fatty acids of CKD control rats were significantly protected by curcumin co-treatment (at the dose of 50, 100 and 150 mg/kg). Furthermore, curcumin significantly increased the serum high-density lipoprotein (HDL) cholesterol compared to the CKD control rats but did not attenuate the CKD-induced weight retardation. Mathematical computational analysis revealed that curcumin significantly reduced indicators for the risk of atherosclerotic lesions (atherogenic index) and coronary atherogenesis (coronary risk index). In addition, curcumin improved kidney function as shown by the reduction in proteinuria and improvement in creatinine clearance.ConclusionThe results provide new scientific evidence for the use of curcumin in CKD-associated dyslipidaemia and substantiates the traditional use of curcumin in preventing kidney damage.

Retrospective Analysis of Modified Hyper-CVAD Therapy Combined with Proteasome Inhibition for Patients with Multiple Myeloma and Renal Insufficiency or Renal Failure

Background: While novel agents have allowed for successful outpatient treatment of patients with multiple myeloma (MM), multi-agent infusional chemotherapy regimens continue to have a role, particularly in high burden disease states. However, the use of platinum-based regimens is limited in patients with renal insufficiency and renal failure. We have been using a modified hyperCVAD regimen, termed HyperCD (Table 1), with omission of vincristine, and inclusion of a proteasome inhibitor (PI, either bortezomib or carfilzomib) in these aggressive clinical presentations for rapid tumor reduction. Here we present our experience with this treatment modality, with analysis of treatment outcomes and toxicities in the renal insufficiency subset.Methods:We performed a single-center chart review of all MM patients at our institution with available electronic medical records who received at least one HyperCD cycle in the setting of concurrent renal insufficiency (defined by estimated eGFR <50mL/min by CKD-EPI at treatment start) between 01/2012 and 12/2016. Data on demographics and disease characteristics were collected. Response was determined by IMWG criteria. Progression free survival (PFS) and overall survival (OS) were calculated by Kaplan Meier method, with PFS including progression or death from any cause and censoring at last known follow-up for live patients.Results:Baseline characteristics: Sixty-seven patients were included in this analysis (Table 2), including 46 non-dialysis dependent and 21 dialysis dependent patients. Median age was 62 years (range 29 - 85). 19% had known prior high-risk cytogenetics defined by t(4;14), t(14;16) and/or 17p(del). Median number of prior lines of therapy was 2 (range 0-14). 34% had prior autologous transplantation. Prior therapies included alkylator therapy in 67%, immunomodulator in 64%, anti-CD38 antibody therapy in 13%, and PI in 87%. Reasons for HyperCD administration included rapidly progressive disease (63%), hypercalcemia (30%), extensive bony (16%) or soft tissue disease (9%), primary (4%) or secondary plasma cell leukemia (7%), and stem cell mobilization (22%). Disease status at time of treatment included new diagnosis (13%), insufficient prior response (18%), and relapsed/refractory or relapsed disease (69%). The median number of cycles administered per patient was 1 (range 1-4), with 55% receiving 1 cycle and 45% receiving 2 or more cycles. The median creatinine at therapy start was 2.93 (range 1.15-8.98).Responses: Of 23 patients on dialysis, 8 (35%) were able to discontinue either during or sometime after therapy. Median percent improvement in creatinine after therapy among non-dialysis patients was 24% (p=0.0001 by wilcoxon signed rank). The overall response rate (ORR) was 69% (46/67), with 1% complete responses (CR), 28% very good partial responses (VGPR), and 39% partial responses (PR). The median time to PR or better was 1.1 months, with a median PFS of 5.1 months, and median OS of 21 months. 87% of patients were able to bridge to other therapy including autologous transplantation (22%). 81% of patients have progressed or died at last follow-up, with disease being the most common cause of death (29/34, 85%).Therapy related toxicities: Median duration of severe neutropenia (ANC</=500/µl) was 4 days (range 0-17) and severe thrombocytopenia (platelets </= 50,000/µl) 7 days (range 0-29), per cycle. 24% of patients had neutropenic fever with documented infections in 37%. Other toxicities included severe bleeding (4%), deep vein thrombosis (7%), and cardiac events (25%), including tachyarrhythmia (9%), demand ischemia (3%), heart failure (2%), pulmonary hypertension (3%), and volume overload (9%). One patient (2%) had potential treatment related mortality (TRM) approximately 3 months after therapy and 1 patient (2%) died within 30 days from progressive disease.Conclusion: HyperCD-based regimens yielded relatively high response rates in MM patients with renal insufficiency, including renal failure. Several patients discontinued dialysis, with improvement in renal function also seen in non-dialysis patients. While TRM was low, hematologic, infectious, and cardiac toxicities were common. The majority of patients were able to successfully bridge to other therapy. HyperCD-based regimens may thus be a potential alternative to platinum based therapies in myeloma patients requiring intensive infusional chemotherapy. [Display omitted] DisclosuresShah:Nekktar: Consultancy; Teneobio: Consultancy; Amgen: Consultancy; Sutro Biopharma: Research Funding; Janssen: Research Funding; Nkarta: Consultancy; Indapta Therapeutics: Equity Ownership; Takeda: Consultancy; Celgene: Research Funding; Indapta Therapeutics: Consultancy; Bluebird: Research Funding; University of California San Francisco: Employment; Kite: Consultancy; Sanofi: Consultancy; Bristol Myers Squibb: Consultancy. Wong:Janssen: Research Funding; Roche: Research Funding. Martin:Sanofi: Research Funding; Amgen: Research Funding; Roche: Consultancy. Wolf:Amgen: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Novartis: Consultancy.

Case report: de novo ANCA-associated vasculitis after kidney transplantation treated with rituximab and plasma exchange

BackgroundAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis causes end-stage renal failure in up to a third of cases even with treatment. The disease recurs occasionally after kidney transplantation, but new onset of ANCA-associated vasculitis after transplantation is highly unusual. The use of rituximab or plasmapheresis for de novo disease after transplantation has not previously been reported.Case presentationRoutine post-transplant follow-up for a 66-year old asymptomatic woman revealed a rise in creatinine from 1.8 to 2.6 mg/dl and increased proteinuria. She had received a cadaveric kidney transplant 20 months previously for end-stage autosomal dominant polycystic kidney disease. Renal allograft biopsy unexpectedly demonstrated pauci-immune glomerulonephritis with extracapillary proliferation and interstitial inflammation. Concurrent serum tested strongly positive for ANCA specific to proteinase 3 (PR3), but stored pre- and post-transplantation serum samples tested negative. These findings established a diagnosis of de novo ANCA-associated vasculitis in the renal allograft.We started treatment with high-dose corticosteroid and rituximab. Despite this, serum creatinine continued to rise and glomerulonephritis remained active in a repeat biopsy. Escalation of the treatment with seven sessions of plasmapheresis led to a temporary improvement in creatinine. No further features of vasculitis emerged and PR3-ANCA titres declined. However, multiple infections complicated the recovery period and were associated with progressive loss of renal transplant function. Four months after the index presentation, transplant function became insufficient and dialysis was restarted.ConclusionsDe novo ANCA-associated vasculitis after renal transplantation is exceptionally rare. It poses a significant risk to graft survival even in the context of intensified immunosuppression. Management relies on clinical evidence from populations with native renal function, yet post-transplant patients may be at increased risk of treatment-related adverse events. Precautions against these risks are crucial in the delivery of care.

3:09 PM Abstract No. 152 Safety and efficacy of angioplasty and/or stenting for transplant renal artery stenosis

Transplant renal artery stenosis (TRAS) is a complication that becomes evident within 3 months to 2 years of transplant. The most common location is the anastomotic site, which can lead to allograft failure, refractory hypertension and fluid retention. Percutaneous transluminal angioplasty is the mainstay of treatment. The aim of this study is to assess the safety, technical factors and efficacy of angioplasty and/or stenting in TRAS. This is a single-center retrospective study of all cases of transplant renal artery angioplasty/stenting from 2015-17. Using CPT codes, 81 cases were retrieved, of which 21 cases were selected for the study. Data was retrieved from electronic medical records and PACS. Paired sample t-tests were used for statistical analyses. CO2 contrast was used for all angiography except for the final measurement angiogram prior to and during stent placement. Iodinated contrast volume was restricted to less than 10 mL in all cases. One case was done with CO2 alone. Out of 21 patients, 12 were females and the mean age was 58.9 years (SD 8). Angioplasty alone was done in 9 patients and stenting was done in 12 patients. Mean angioplasty balloon diameter was 4 mm. Mean stent diameter was 4.7 mm. The mean peak systolic velocity (PSV) in the renal artery prior to intervention was 443.7cm/s (SD 104.0) which decreased to 252.0 cm/s (SD 134.4) at a follow-up duration within one month (p<0.001). The mean creatinine prior to intervention was 2.83 mg/dL (SD 1.2) which decreased to 1.81 mg/dL (SD 1.04) at a follow-up duration within 6 weeks (p<0.001). The mean decrease in PSV was 43% (SD 24.5) and the mean fall in creatinine was 35.2% (SD 18.3). The mean improvement in stenosis post intervention was 130% (SD 95). There was no significant correlation between the improvement in stenosis and the improvement in creatinine or PSV (p = 0.38 and p = 0.47 respectively). There were no complications experienced with any of the 21 patient interventions. Angioplasty and stenting is a safe and effective treatment for transplant renal arterial anastomotic stenosis, which significantly improves blood flow and renal function with minimal use of iodinated contrast agents.

Outcomes in necrotizing soft tissue infections treated with therapeutic plasma exchange.

Treatment of necrotizing soft tissue infections (NSTIs) includes prompt surgical debridement and antibiotics, but despite standard care, the morbidity and mortality remain high. Since therapeutic plasma exchange (TPE) has been considered for treatment of severe sepsis, this study evaluates the efficacy of TPE for patients with NSTI. This is a retrospective study of patients with diagnosis of NSTI who received treatment with and without TPE over an 11-year period. The primary outcome was in-hospital mortality. Fifty-two patients with NSTI treated with TPE (TPE group) and 125 patients with NSTI not treated with TPE (non-TPE group) were assessed. Nineteen (36.5%) patients died in the TPE group, and 35 (28%) patients died in the non-TPE group. Within the TPE group, there was significant improvement in white blood cell (WBC) count and sodium levels 7 days after TPE treatment, but no improvement in creatinine. Inverse probability weighting based on propensity scores was used to compare survival in the TPE and non-TPE groups and demonstrated that TPE was associated with an increased odds of death (odds ratio,2.8). A second analysis matched for six variables yielded 31 pairs and demonstrated no significant difference in mortality or length of stay. This study describes the largest series of patients with NSTIs treated with TPE and showed no evidence of clinical benefit. Further carefully designed studies with meaningful clinical endpoints would prove useful in assessing reproducibility and determining if there is a role for TPE in other forms of severe sepsis.

387 - Early Results of Phase II Study Using OMS721 in Patients with Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HCT-TMA)

Introduction: TMA is a potentially life-threatening complication of HCT currently managed largely by amelioration of inciting factors including avoidance of calcineurininhibitors and treatment of ongoing infections, as well as supportive measures such as hemodialysis. Patients who do not respond have poor prognosis. Plasma exchange has not shown efficacy and no other therapy is approved. Complement activation has been reported in the pathogenesis of HCT-TMA. OMS721 is a human monoclonal IgG4 inhibitor of mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of complement activation. Here we report early results of OMS721 treatment in HCT-TMA patients. Methods: This is a Phase 2 uncontrolled, open-label, 3-stage study of OMS721 to assess safety, tolerability and clinical activity of OMS721 in patients with TMA (HCT-TMA, aHUS and TTP). Stage 1 included dose-escalation cohorts, Stage 2 expands disease-specific cohorts and Stage 3 provides optional extended treatment. For inclusion, patients with HCT-TMA should demonstrate thrombocytopenia and evidence of microangiopathic hemolytic anemia, and at least 2 weeks must have elapsed since changes in immunosuppressive treatment. HCT-TMA patients received OMS721 X *Dose is confidential.*Dose is confidential. mg/kg IV once weekly (Stage 1 up to 4 weeks and Stages 2 and 3 up to 8 weeks). Patients could receive additional half doses if given plasma therapy. Results: 5 HCT-TMA patients were enrolled; 2 patients entered Stage 1 and 3 patients entered Stages 2 and 3. All patients were adults and received HCT for hematological malignancies. Figure 1, Figure 2, Figure 3 provide the change from baseline in TMA variables. These figures provide data on all 5 patients, two of whom discontinued the study (1 each in Stage 1 and Stage 2, both after 2-3 weeks) with one subsequently relapsing and the other receiving palliative care.Figure 2LDH change from baseline over time.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Change in haptoglobin over time.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Statistically significant improvement in LDH and haptoglobin were observed during treatment. Platelet count improved but did not reach statistical significance in this small number of patients. Of the 3 patients who completed treatment, 1 did not show improvement in creatinine but was receiving concomitant nephrotoxic agents; RRT was not required. Creatinine improved or remained normal in the other 2 patients. On extended follow up, 1 patient experienced graft failure and is awaiting a second transplant. The other 2 patients remain stable. OMS721 treatment was well tolerated with no safety concerns. Conclusions: OMS721 improved TMA markers in HCT patients who had not responded to conservative measures. No toxicity signals were observed during treatment. By inhibiting the lectin pathway, OMS721 may be beneficial in the treatment of HCT-TMA and further study is ongoing.

Systematic review with meta-analysis: vasoactive drugs for the treatment of hepatorenal syndrome type 1.

Hepatorenal syndrome type 1 (HRS1) is a functional, rapidly progressive, potentially reversible form of acute kidney injury occurring in patients with cirrhosis. Characterised by intense renal arterial vasoconstriction, it carries a very poor prognosis. There is a significant unmet need for a widely approved, safe and effective pharmacological treatment. To re-evaluate efficacy and safety of pharmacological treatments for HRS1, in the light of recently published randomised controlled trials (RCTs). MEDLINE (OvidSP), EMBASE, PubMed and Cochrane registers were searched for RCTs reporting efficacy and adverse events related to pharmacological treatment of HRS1. Search terms included: 'hepatorenal syndrome', 'terlipressin', 'noradrenaline', 'octreotide', 'midodrine', 'vasopressin', 'dopamine', 'albumin' and synonyms. Comparison of vasoactive drugs vs. placebo/no treatment, and two active drugs were included. Meta-analysis was performed for HRS1 reversal, creatinine improvement, mortality and adverse events. Twelve RCTs enrolling 700 HRS1 patients were included. Treatment with terlipressin and albumin led to HRS1 reversal more frequently than albumin alone or placebo (RR: 2.54, 95% CI: 1.51-4.26). Noradrenaline was effective in reversing HRS1, but trials were small and nonblinded. Overall, there was mortality benefit with terlipressin (RR: 0.79, 95% CI: 0.63-1.01), but sensitivity analysis including only trials with low risk of selection bias weakened this relationship (RR: 0.87, 95% CI: 0.71-1.06). Notably, there was a significant risk of adverse events with terlipressin therapy (RR: 4.32, 95% CI: 0.75-24.86). Terlipressin treatment is superior to placebo for achieving HRS1 reversal, but mortality benefit is less clear. Terlipressin is associated with significant adverse events, but infusion regimens may be better tolerated. There is continued need for safe and effective treatment options for hepatorenal syndrome.

IVC Measurements in Critically Ill Patients with Acute Renal Failure.

Objective To determine whether the inferior vena cava (IVC) measurement by bedside ultrasound (US-IVC) predicts improvement in renal function in patients with acute kidney injury (AKI). Design Prospective observational study. Setting Medical intensive care unit. Patients 33 patients with AKI were included. Intervention US-IVC was done on admission. The patients' management was done by the primary teams, who were unaware of the US-IVC findings. Two groups of patients were identified. Group 1 included patients who were managed in concordance with their US-IVC (potential volume responders who had a positive fluid balance at 48 h after admission and potential volume nonresponders who had an even or negative fluid balance at 48 hours after admission). Group 2 included patients in whom the fluid management was discordant with their US-IVC. Measurements and Main Results At 48 hours, Group 1 patients had a greater improvement in creatinine [85% versus 31%, p = 0.0002], creatinine clearance (78 ± 93% versus 8 ± 64%, p = 0.002), and urine output (0.86 ± 0.54 versus 0.45 ± 0.36 ml/Kg/h, p = 0.03). Conclusion In critically ill patients with AKI, concurrence of fluid therapy with IVC predicted fluid management, as assessed by bedside ultrasound, was associated with improved renal function at 48 hours. This trial is registered with ClinicalTrials.gov registration number: NCT02064244.

Effects of ventriculoarterial coupling changes on renal function, echocardiographic indices and energy efficiency in patients with acute decompensated systolic heart failure under furosemide and dopamine treatment: A comparison of three therapeutic protocols

BackgroundVentriculoarterial coupling (VAC) status relates to tissue perfusion and its optimization may improve organ function and energy efficiency (EE) of the cardiovascular system. The effects of non-invasively calculated VAC improvement on echocardiographic parameters, renal function indices and EE improvement in patients with acute decompensated systolic heart failure were studied. Furthermore, effects of different treatment modalities on VAC, renal function and echocardiographic parameters were compared. MethodsSystolic heart failure patients with ejection fraction <50% were studied, who, at the treating physician's discretion, received 8-hour infusions of: high dose furosemide (20mg/h), low dose furosemide (5mg/h) or dopamine (5μg/kg/min) combined with furosemide (5mg/h). Echocardiographic assessments were performed at 0 and 24h. Renal function was evaluated using serum creatinine and creatinine clearance. VAC and EE were assessed noninvasively, by echocardiography. ResultsSignificant correlations were noted between VAC improvement and improvements in EE and serum creatinine (rho=0.96, p<0.001, rho=0.32, p=0.04 respectively). Dopamine–furosemide combination had a borderline effect on creatinine (p=0.08) and led to significant improvements in e′, E/e′ ratio (p=0.015 and p=0.009 respectively) and VAC (value closer to 1). ConclusionVAC improvement correlated with EE and creatinine improvement, regardless of treatment, supporting a potential role for VAC status assessment and improvement in acute decompensated systolic heart failure. Dopamine and furosemide combination seemed to improve VAC and diastolic function but only had a borderline effect on renal function.

Differentiating malignant hypertension-induced thrombotic microangiopathy from thrombotic thrombocytopenic purpura.

Malignant hypertension can cause thrombotic microangiopathy (TMA) and the overall presentation may mimic thrombotic thrombocytopenic purpura (TTP). This presents a dilemma of whether or not to initiate plasma exchange. The objective of the study was to determine the clinical and laboratory manifestations of malignant hypertension-induced TMA, and its outcomes. Using several search terms, we reviewed English language articles on malignant hypertension-induced TMA, indexed in MEDLINE by 31 December 2013. We also report a new case. All these cases were analyzed using descriptive statistics. A total of 19 patients, with 10 males, had a median age of 38 years at diagnosis; 58% had a history of hypertension. Mean arterial pressure at presentation was 159 mmHg (range 123-190 mmHg). All had prominent renal dysfunction (mean creatinine of 5.2 mg/dl, range 1.7-13 mg/dl) but relatively modest thrombocytopenia (mean platelet count of 60 × 103/µl, range 12-131 × 10(3)/µl). Reported cases (n = 9) mostly had preserved ADAMTS-13 activity (mean 64%, range 18-96%). Following blood pressure control, the majority had improvement in presenting symptoms (100%) and platelet counts (84%); however, only 58% had significant improvement in creatinine. More than half (53%) needed hemodialysis. One patient died of cardiac arrest during pacemaker insertion. Prior history of hypertension, high mean arterial pressure, significant renal impairment but relatively modest thrombocytopenia and lack of severe ADAMTS-13 deficiency (activity <10%) at diagnosis are clues to diagnose malignant hypertension-induced TMA. Patients with malignant hypertension respond well to antihypertensive agents and have favorable nonrenal outcomes.

Protective Role of Raw-Turmeric Rhizomes Against Nicotine-Induced Complications of Beedi (Indian Cigarette) Workers

Introduction: The unscientific process of beedi (Indian smoking element) production under constant exposure of nicotine dust in India induces serious health disorders to the workers. Beedi produces more tar in smoke than cigarette due to lack of any filtering process. Sometimes active consumption of beedi and other tobacco products makes the users more vulnerable to cancer, respiratory diseases and cardiovascular disorders etc. Objective: The present study was designed to observe the protective effects of raw turmeric rhizomes on health conditions of the beedi workers who were exposed to nicotine dust for 8-10 hours daily for a long duration. Methods: General health checkup, blood glucose levels, lipid profiles and the hemogram profiles etc. of the workers from two beedi factories (Canning of South 24 Parganas District and Bankura of Bankura District, both in West Bengal, India) were conducted before and after the consumption of laboratory processed raw turmeric rhizomes (80 mg/kg body weight/day by chewing) for 8 weeks. Blood samples (5 ml) were collected from all the workers before and after the completion of the study and analyzed for estimation of different parameters. Results: The results showed significant improvement in the general health conditions of the factory workers who consumed raw-turmeric rhizomes. Significant improvement of blood pressure, blood glucose levels and lipid profiles and also improvement of creatinine, serum protein and SGOT/SGPT levels of the treated volunteers were noted. The results also showed improvement in the enzymes levels of SOD, GSH and GPX in the serum of rhizomes consumed workers. Conclusion: It is concluded that turmeric rhizomes are effective in the amelioration of nicotine-induced complications. It would be a better therapeutic supplement for the improvement of health for the workers who are compelled to work under nicotinic dust environment for a long time.

AB0486 The Complete Response in Patients with Lupus Nephritis Treated with Mycophenolate Mofetil (MMF) as Their First Line Therapy

BackgroundThe optimal therapeutic approach for lupus nephritis (LN) involves an induction phase to achieve remission followed by maintenance therapy to prevent relapses. Mycophenolate mofetil (MMF) has become the primary induction...

Perioperative Levosimendan Therapy Improves Renal Function in Heart Transplant Recipients

Purpose We evaluated the effects of perioperative levosimendan therapy on renal function in heart failure patients undergoing heart transplantation. Methods and Materials Of 103 transplant recipients, 56 (53%) received perioperative infusion of levosimendan (0.1 microg/kg/min for 24 hours; LS Group), and 47 (47%) received no levosimendan (Controls). Renal function was assessed pre-transplantation and 1 week thereafter. Results At the time of transplantation, the groups did not differ in age (53±11 years in the LS group vs. 49±14 years in Controls; P=0.07), gender (male: 77% vs. 79%; P=0.82), heart failure etiology (ischemic: 28% vs. 27%; P=0.73), or donor age (41±11 years vs. 38±12 years; P=0.2). Similarly, there was no difference in creatinine (134±126 μmol/L in LS Group vs. 115±72 μmol/L in Controls; P=0.53) and creatinine clearance (Ccr) (84±42 mL/min vs. 83±34 mL/min;P=0.91). At 1 week after transplantation, we found a decrease in creatinine and an increase in Ccr in LS Group, but not in Controls despite similar mean arterial pressure in both groups (76±10 mmHg in LS Group vs. 79±20 mmHg in Controls; P=0.39). This led to a significant intergroup difference in creatinine (79±37 μmol/L in LS Group vs. 107±50 μmol/L in Controls; P=0.02) and Ccr (110±48 mL/min vs. 83±40 mL/min; P=0.005). An improvement in creatinine ≥50 μmol/L occurred in 22 % of patients from LS Group; compared with 5 % of Controls (P=0.01). Conclusions In patients undergoing heart transplantation perioperative levosimendan therapy improves post-transplant renal function. Since impaired renal function is a predictor of adverse outcome, perioperative levosimendan use could improve prognosis of heart transplant recipients.

Melanotan II injection resulting in systemic toxicity and rhabdomyolysis

Introduction. Melanotan products are currently purchased over the Internet and are designed to induce melanogenesis to create sunless tanning as well are used as sexual stimulants. We report a novel case of systemic toxicity with sympathomimetic excess and rhabdomyolysis after use of Melanotan II. Case report. A 39 year-old Caucasian male injected subcutaneously 6 mg of Melanotan II purchased over the Internet in an attempt to darken his skin during wintertime. This dose was six times the recommended starting dose per the patient. In the emergency department two hours post injection, he complained of diffuse body aches, sweating, and a sensation of anxiety. Vital signs included BP 151/85 mmHg, HR 130 bpm that peaked at 146 bpm, and temperature of 97.8°F. Physical exam demonstrated a restless and anxious appearing male with mydriasis, diaphoresis, tachycardia, and diffuse muscle tremors. Pertinent laboratory values were creatinine 2.25 mg/dL, CPK 1760 IU/L, troponin 0.23 ng/mL, WBC 19.1 k/μL. Urinalysis demonstrated 3 + blood with red cell casts but 0–2 RBC/hpf. Qualitative urine drug screen was negative for metabolites of cocaine and amphetamines but positive for opiates. The patient received benzodiazepines for agitation and anxiety and had improvement in his symptoms. He was admitted to the ICU and during hospitalization his CPK elevated to 17773 IU/L 12 hours later. He continued to receive intravenous fluids with sodium bicarbonate for rhabdomyolysis and his CPK decreased to 2622 IU/L with improvement of creatinine to 1.23 mg/dL upon discharge from the ICU after 3 days. The substance, which he injected, was analyzed via mass spectrometry and was confirmed to be Melanotan II when compared with an industry purchased standard sample. Discussion. Melanotan products are purchased via the Internet and have three main formulations (Melanotan I, Melanotan II, and bremelanotide). Melanotan I increases melanogenesis and eumelanin content to produce sunless tanning. Melanotan II also increases skin pigmentation but also produces spontaneous penile erections and sexual stimulation. Bremelanotide is a variation of Melanotan II that is specifically designed for sexual stimulation. This unique case highlights the potential of systemic toxicity with sympathomimetic excess, rhabdomyolysis, and renal dysfunction from Melanotan II use. Conclusion. Melanotan II use resulted in systemic toxicity including apparent sympathomimetic symptoms, rhabdomyolysis, and renal dysfunction.

Eculizumab for Dense Deposit Disease and C3 Glomerulonephritis

The principle defect in dense deposit disease and C3 glomerulonephritis is hyperactivity of the alternative complement pathway. Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex, may prove beneficial. In this open-label, proof of concept efficacy and safety study, six subjects with dense deposit disease or C3 glomerulonephritis were treated with eculizumab every other week for 1 year. All had proteinuria >1 g/d and/or AKI at enrollment. Subjects underwent biopsy before enrollment and repeat biopsy at the 1-year mark. The subjects included three patients with dense deposit disease (including one patient with recurrent dense deposit disease in allograft) and three patients with C3 glomerulonephritis (including two patients with recurrent C3 glomerulonephritis in allograft). Genetic and complement function testing revealed a mutation in CFH and MCP in one subject each, C3 nephritic factor in three subjects, and elevated levels of serum membrane attack complex in three subjects. After 12 months, two subjects showed significantly reduced serum creatinine, one subject achieved marked reduction in proteinuria, and one subject had stable laboratory parameters but histopathologic improvements. Elevated serum membrane attack complex levels normalized on therapy and paralleled improvements in creatinine and proteinuria. Clinical and histopathologic data suggest a response to eculizumab in some but not all subjects with dense deposit disease and C3 glomerulonephritis. Elevation of serum membrane attack complex before treatment may predict response. Additional research is needed to define the subgroup of dense deposit disease/C3 glomerulonephritis patients in whom eculizumab therapy can be considered.

Conversion to Proliferation Signal Inhibitors–Based Immunosuppressive Regimen in Kidney Transplantation: To Whom and When?

Background Despite significant advances in kidney transplantation, long-term graft survival has not dramatically improved leading to strategies to change immunosuppression during the posttransplantation period. Proliferation signal inhibitors (PSI) sirolimus or everolimus possess immunosuppressive and antiproliferative properties. Methods We evaluated 62 kidney transplant recipients who underwent conversion from a calcineurin inhibitors (CNI)– to a PSI-based regimen for various reasons. The statistical analysis used SPSS v.15.0 software. We compared calculated glomerular filtration rates (GFRs) before initiation of PSI (baseline) and at 6 months after conversion. Results We converted to a PSI-based triple regimen at 172.0 ± 116.5 days after transplantation. The mean serum creatinine at the time of conversion was 2.0 ± 1.1 mg/dL, and it was 1.5 ± 0.7 mg/dL at 6 months after conversion. The rate of change in serum creatinine was −17.1 ± 23.5%. The mean calculated GFR at the time of conversion was 53.6 ± 25.5 mL/min and at 6 months after conversion was 65.8 ± 23.7 mL/min. The rate of change in calculated GFR was 37.9 ± 71.7% (16.4/59.4) at 6 months. Thus we observed significant improvements in creatinine and GFR ( P values <.001) after conversion. The Improved GFR significantly correlated with prior dialysis duration and time to conversion ( P = .025; P = .012). Patients who had a shorter duration on dialysis and shorter time to conversion experienced more benefit from conversion. Four of the 62 patients reported gastrointestinal toxicity, which resolved with dose reduction in 3 patients: 15 patients experienced acne; 16 reported oral ulcers. None of these toxicities resulted in discontinuation of PSI therapy. Serum cholesterol and tryglyceride levels tended to increase among the conversion group, but they did not show statistical significance. Conclusion We observed that minimization or withdrawal of CNI with addition of a PSI was a good treatment for deterioration of renal allograft function.

Percutaneous nephrolithotomy for complex caliceal and staghorn stones in patients with solitary kidney

Treatment of patients with solitary kidney having complex stones is one of the most challenging problem in urology. We present our experience with percutaneous nephrolithotomy (PCNL) in treating 16 patients with staghorn stones in a solitary kidney to determine long-term renal functional results. We retrospectively reviewed the records of 16 patients with complex caliceal or staghorn stones in a solitary kidney treated with PCNL. Demographic data, number and location of accesses, hemoglobin values, stone analyses, and complications were studied. Serum creatinine, glomerular filtration rate (GFR), systolic and diastolic blood pressure, new onset hypertension, and kidney morphology were determined preoperatively and postoperatively at 1month and 1year. Male to female ratio was 14:2 and mean age was 49.6years (range 31-55). Of these, 10 (62.5%) patients required a single tract, while 6 (37.5%) required multiple tracts. The calculi were extracted or fragmented successfully in 13 (81.3%) patients and complete stone clearance was achieved after the first stage. In two patients with residual calculi, a double-J catheter was inserted and extracorporeal shock wave lithotripsy (SWL) was performed. There were no significant intraoperative problems except in one patient, who had bleeding from an infundibular tear attributable to torquing. During the 1-year study period, none of the patients progressed to end-stage renal disease requiring dialysis. We demonstrated a significant improvement in creatinine and GFR levels from preoperatively to 1-year follow-up. The number of patients with hypertension before PCNL was 5 and by the end of follow-up there was no new onset hypertension. The demonstrated effectiveness, small number of complications at short-term, not any poorly effect on renal function and blood pressure at the long-term follow-up confirm that PCNL is not only effective but is also safe in the solitary kidney with staghorn calculi.

127: No Improvement in Creatinine Despite Dialysis When Poisoned

127: No Improvement in Creatinine Despite Dialysis When Poisoned