Soc Nephrol Research Articles

Hemodialysis With 3% Normal Saline: An Uncommon Treatment to Reduce Risk of Cerebral Edema in Severe Hypernatremia Secondary to Parathyroid Carcinoma

SESSION TITLE: Critical Care 5 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Hemodialysis (HD) has been used as a treatment for acidosis, refractory hyperkalemia, intoxications, fluid overload and uremia. Diverse etiologies of electrolytes disturbances have been reported which require HD, but few cases of hypernatremia with hypercalcemia secondary to parathyroid carcinoma have been reported. CASE PRESENTATION: A 65 y/o F with past medical history of HTN, CKD, nephrolithiasis, andhypothyroidism presented to the ER with abdominal pain and general weakness since 5 days ago. Vital signs: BP: 153/83 mmHg, P: 125 bpm,T: 36.4 oC. Physical examination was remarkable for dry oral mucosa, epigastric tenderness on palpation and non-pitting bilateral leg edema +2. Laboratories results demonstrated hypercalcemia and hypernatremia(Table 1). After 3 days, she developed hypoactivity and altered mental status. Patient was transfer to intensive care unit. Laboratories were repeated (Table 2). Severe hypercalcemia lead to nephrogenic diabetes insipidus (NDI) which induced uremia and volume depleted hypernatremia. Emergency HD with F160, Dialysate flow rate (DFR): 500, Blood flow rate (BFR): 200 and Dialysate: K: 2.4 mEq/l, Ca: 2.7 mEq/l, CO2: 29 mEq/l, Na: 155 mEq/l and 3% saline was administered. The patient improved uremia and hypernatremia after receiving 10 HD treatment with 3% saline. Laboratories afterwards were Na: 139 mmol/L, CO2: 27.5 mmol/L, BUN: 18.5 mg/dL, Cr: 4.98 mg/dL, Ca: 11.8 mg/dL. A parathyroid adenoma was found with ultrasound and was removed, revealing a parathyroid carcinoma. DISCUSSION: Volume depleted hypernatremia is a complication of NDI. NDI is an impaired urinary concentrating ability due to resistance of antidiuretic hormone in the V2 receptors of the collecting tubules or interference with the countercurrent mechanism due to medullary injury. This becomes clinically apparent when calcium levels are above 11 mg/dL, as in our case with parathyroid carcinoma. This patient with, hypernatremia and uremic syndrome was treated with HD 3% saline to reduce mortality risk associated with cerebral edema, correcting serum sodium at an initial rate of 2-3 mEq/L/h. Patient completed treatment without usual neurological changes associated with cerebral edema. CONCLUSIONS: This case presents an unusual treatment for the rare cases of parathyroid carcinoma associated with hypernatremia treated with HD 3% normal saline to reduce risk cerebral edema. Reference #1: Bhave G, Neilson EG. Body fluid dynamics: back to the future. J Am Soc Nephrol. 2011 Dec. 22(12):2166-81. Reference #2: Darmon M, Timsit JF, Francais A, et al. Association between hypernatraemia acquired in the ICU and mortality: a cohort study. Nephrol Dial Transplant. 2010 Feb 17. Reference #3: Schaapveld M, Jorna FH, Aben KK, Haak HR, Plukker JT, Links TP. Incidence and prognosis of parathyroid gland carcinoma: A population-based study in The Netherlands estimating the preoperative diagnosis. Am J Surg. 2011 Aug 20. DISCLOSURE: The following authors have nothing to disclose: Keyla Davila Marcano, Stephen Burry, Jesse Aleman, Luis Ortiz-Heredia, Felix Perez No Product/Research Disclosure Information

Three-Dimensional Cross-Sectional Light-Sheet Microscopy Imaging of the Inflamed Mouse Gut

Three-Dimensional Cross-Sectional Light-Sheet Microscopy Imaging of the Inflamed Mouse Gut

Research roundup

Journal of Kidney CareVol. 2, No. 5 Research RoundupResearch roundupPublished Online:26 Sep 2017https://doi.org/10.12968/jokc.2017.2.5.292AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View articleAbstractIn this section, Nikki Welyczko provides a brief synopsis of a selection of recently published research papers of potential interest to professionals in the kidney community. This research roundup aims to provide an overview, rather than a detailed critique, of the research that is presented. A full reference is provided with each study, should you wish to look at any of the papers in greater detail. References Santana DA, Poortmans JR, Dórea EL, Machado JB de A, Fernandes AL, Sá-Pinto AL et al.. Acute exercise does not impair renal function in nondialysis chronic kidney disease patients regardless of disease stage. Am J Physiol Renal Physiol. 2017;313(2):F547–F552. https://doi.org/https://doi.org/10.1152/ajprenal.00131.2017 Google ScholarNeal B, Perkovic V, Mahaffey KW et al.. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–657. https://doi.org/https://doi.org/10.1056/nejmoa1611925 Google ScholarSimonsen E, Komenda P, Lerner B et al.. Treatment of uremic pruritus: a systematic review. American Journal of Kidney Diseases. 2017. https://doi.org/https://doi.org/10.1053/j.ajkd.2017.05.018 Google ScholarAcedillo RR, Wald R, McArthur E et al.. Characteristics and outcomes of patients discharged fome from an emergency department with AKI. Clin J Am Soc Nephrol. 2017;12(8):1215–1225. https://doi.org/https://doi.org/10.2215/cjn.10431016 Google Scholar FiguresReferencesRelatedDetails 2 September 2017Volume 2Issue 5ISSN (print): 2397-9534ISSN (online): 2397-9542 Metrics History Published online 26 September 2017 Published in print 2 September 2017 Information© MA Healthcare LimitedPDF download

Impact of Protease Inhibitor-Based Anti-Retroviral Therapy on Outcomes for HIV+ Kidney Transplant Recipients.

Excellent outcomes have been demonstrated among select HIV-positive kidney transplant (KT) recipients with well-controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01-10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre- and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non-PI-based ART (88 PI vs. 244 non-PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI-based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p=0.02) than those on non-PI regimens. On adjusted analyses, PI-based regimens were associated with a 1.8-fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22-2.77, p=0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75-11.48, p=0.002), and a 1.9-fold increased risk of death as compared to non-PI regimens (aHR 1.91, 95% CI 1.02-3.59, p=0.05). These results suggest that whenever possible, recipients should be converted to a non-PI regimen prior to kidney transplantation.

Effects of DNA Methylation on Progression to Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Biopsies: A Multi-Omics Approach.

Progressive fibrosis of the interstitium is the dominant final pathway in renal destruction in native and transplanted kidneys. Over time, the continuum of molecular events following immunological and nonimmunological insults lead to interstitial fibrosis and tubular atrophy and culminate in kidney failure. We hypothesize that these insults trigger changes in DNA methylation (DNAm) patterns, which in turn could exacerbate injury and slow down the regeneration processes, leading to fibrosis development and graft dysfunction. Herein, we analyzed biopsy samples from kidney allografts collected 24 months posttransplantation and used an integrative multi-omics approach to understand the underlying molecular mechanisms. The role of DNAm and microRNAs on the graft gene expression was evaluated. Enrichment analyses of differentially methylated CpG sites were performed using GenomeRunner. CpGs were strongly enriched in regions that were variably methylated among tissues, implying high tissue specificity in their regulatory impact. Corresponding to this methylation pattern, gene expression data were related to immune response (activated state) and nephrogenesis (inhibited state). Preimplantation biopsies showed similar DNAm patterns to normal allograft biopsies at 2 years posttransplantation. Our findings demonstrate for the first time a relationship among epigenetic modifications and development of interstitial fibrosis, graft function, and inter-individual variation on long-term outcomes.

Neutrophils in cisplatin AKI—mediator or marker?

Inflammation is an important mediator of most forms of acute kidney injury (AKI). Although neutrophils are prominent components of theinflammatory cascade, the precise role of neutrophils in AKI and the mechanisms by which they contribute to AKI remain controversial. In this issue, Deng etal. identify an important cross talk between renal epithelial cells and neutrophils involving the production and action ofleukotriene B4 in mediating cisplatin AKI. We discuss the possible explanations for the discrepant findings that have been reported for neutrophils in cisplatin AKI.

Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases

The pathophysiology of many proteinuric kidney diseases is poorly understood, and microRNAs (miRs) regulation of these diseases has been largely unexplored. Here, we tested whether miR-378a-3p is a novel regulator of glomerular diseases. MiR-378a-3p has two predicted targets relevant to glomerular function, the glomerular basement membrane matrix component, nephronectin (NPNT), and vascular endothelial growth factor VEGF-A. In zebrafish (Danio rerio), miR-378a-3p mimic injection or npnt knockdown by a morpholino oligomer caused an identical phenotype consisting of edema, proteinuria, podocyte effacement, and widening of the glomerular basement membrane in the lamina rara interna. Zebrafish vegf-A protein could not rescue this phenotype. However, mouse Npnt constructs containing a mutated 3'UTR region prevented the phenotype caused by miR-378a-3p mimic injection. Overexpression of miR-378a-3p in mice confirmed glomerular dysfunction in a mammalian model. Biopsies from patients with focal segmental glomerulosclerosis and membranous nephropathy had increased miR-378a-3p expression and reduced glomerular levels of NPNT. Thus, miR-378a-3p-mediated suppression of the glomerular matrix protein NPNT is a novel mechanism for proteinuria development in active glomerular diseases.

The Role of PET Scanning in the Evaluation of Patients With Kidney Disease.

Patients with underlying kidney disease are often required to undergo imaging for a variety of purposes including diagnosis and prognosis. A test that is being increasingly used with for this group of patients is the positron emission test (PET) scan. In addition, combining the nuclear medicine technique (PET) with computed tomography scan allows additional imaging advantages over either alone. These imaging modalities are commonly used for a number of extrarenal indications (ie, cancer, coronary artery disease, central nervous system disease, infectious diseases, and others). They have also been used for diagnosis of acute tubulointerstitial nephritis, evaluation and management of retroperitoneal fibrosis, identifying infection within kidney and liver cysts, and distinguishing complex kidney cysts from kidney cancer in patients with underlying CKD. We will review PET scan utility in patients with kidney disease.

Quiz: Acute Kidney Injury in a Patient on a TNF-α Blocking Agent

Quiz: Acute Kidney Injury in a Patient on a TNF-α Blocking Agent

Inflammation and Fibrosis in Polycystic Kidney Disease.

Polycystic kidney disease (PKD) is a commonly inherited disorder characterized by cyst formation and fibrosis (Wilson, N Engl J Med 350:151-164, 2004) and is caused by mutations in cilia or cilia-related proteins, such as polycystin 1 or 2 (Oh and Katsanis, Development 139:443-448, 2012; Kotsis et al., Nephrol Dial Transplant 28:518-526, 2013). A major pathological feature of PKD is the development of interstitial inflammation and fibrosis with an associated accumulation of inflammatory cells (Grantham, N Engl J Med 359:1477-1485, 2008; Zeier et al., Kidney Int 42:1259-1265, 1992; Ibrahim, Sci World J 7:1757-1767, 2007). It is unclear whether inflammation is a driving force for cyst formation or a consequence of the pathology (Ta et al., Nephrology 18:317-330, 2013) as in some murine models cysts are present prior to the increase in inflammatory cells (Phillips et al., Kidney Blood Press Res 30:129-144, 2007; Takahashi et al., J Am Soc Nephrol JASN 1:980-989, 1991), while in other models the increase in inflammatory cells is present prior to or coincident with cyst initiation (Cowley et al., Kidney Int 43:522-534, 1993, Kidney Int 60:2087-2096, 2001). Additional support for inflammation as an important contributor to cystic kidney disease is the increased expression of many pro-inflammatory cytokines in murine models and human patients with cystic kidney disease (Karihaloo et al., J Am Soc Nephrol JASN 22:1809-1814, 2011; Swenson-Fields et al., Kidney Int, 2013; Li et al., Nat Med 14:863-868, 2008a). Based on these data, an emerging model in the field is that disruption of primary cilia on tubule epithelial cells leads to abnormal cytokine cross talk between the epithelium and the inflammatory cells contributing to cyst growth and fibrosis (Ta et al., Nephrology 18:317-330, 2013). These cytokines are produced by interstitial fibroblasts, inflammatory cells, and tubule epithelial cells and activate multiple pathways including the JAK-STAT and NF-κB signaling (Qin et al., J Am Soc Nephrol JASN 23:1309-1318, 2012; Park et al., Am J Nephrol 32:169-178, 2010; Bhunia et al., Cell 109:157-168, 2002). Indeed, inflammatory cells are responsible for producing several of the pro-fibrotic growth factors observed in PKD patients with fibrosis (Nakamura et al., Am J Nephrol 20:32-36, 2000; Wilson et al., J Cell Physiol 150:360-369, 1992; Song et al., Hum Mol Genet 18:2328-2343, 2009; Schieren et al., Nephrol Dial Transplant 21:1816-1824, 2006). These growth factors trigger epithelial cell proliferation and myofibroblast activation that stimulate the production of extracellular matrix (ECM) genes including collagen types 1 and 3 and fibronectin, leading to reduced glomerular function with approximately 50% of ADPKD patients progressing to end-stage renal disease (ESRD). Therefore, treatments designed to reduce inflammation and slow the rate of fibrosis are becoming important targets that hold promise to improve patient life span and quality of life. In fact, recent studies in several PKD mouse models indicate that depletion of macrophages reduces cyst severity. In this chapter, we review the potential mechanisms of interstitial inflammation in PKD with a focus on ADPKD and discuss the role of interstitial inflammation in progression to fibrosis and ESRD.

Would prescribing target Kt dose adjusted for body surface area improve hemodialysis outcomes?

The use of Kt/V to prescribe and monitor hemodialysis adequacy remains the current standard, although it is increasingly questioned. Alternative proposals for dose prescription and monitoring have been advocated. In a noninterventional, prospective study reported in this issue, Maduell etal., utilizing online ionic dialysance, explore the association between outcome measures (mortality and hospitalization rates) and the extent to which delivered Kt dose achieved minimal target Kt doses calculated from individual estimates of body surface area.

Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53.

BackgroundAboriginal Australians are at high risk of cardiovascular, metabolic and renal diseases, resulting in a marked reduction in life expectancy when compared to the rest of the Australian population. This is partly due to recognized environmental and lifestyle risk factors, but a contribution of genetic susceptibility is also likely.MethodsUsing results from a comprehensive survey of one community (N = 1350 examined individuals), we have tested for familial aggregation of plasma glucose, arterial blood pressure, albuminuria (measured as urinary albumin to creatinine ratio, UACR) and estimated glomerular filtration rate (eGFR), and quantified the contribution of variation at four candidate genes (ACE; TP53; ENOS3; MTHFR).ResultsIn the subsample of 357 individuals with complete genotype and phenotype data we showed that both UACR (h2 = 64%) and blood pressure (sBP h2 = 29%, dBP, h2 = 11%) were significantly heritable. The ACE insertion-deletion (P = 0.0009) and TP53 codon72 polymorphisms (P = 0.003) together contributed approximately 15% of the total heritability of UACR, with an effect of ACE genotype on BP also clearly evident.ConclusionsWhile the effects of the ACE insertion-deletion on risk of renal disease (especially in the setting of diabetes) are well recognized, this is only the second study to implicate p53 genotype as a risk factor for albuminuria - the other being an earlier study we performed in a different Aboriginal community (McDonald et al., J Am Soc Nephrol 13: 677-83, 2002). We conclude that there are significant genetic contributions to the high prevalence of chronic diseases observed in this population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0396-2) contains supplementary material, which is available to authorized users.

A More Focused Approach to Phosphorus Nutrition Education for the Adolescent Kidney Patient.

A More Focused Approach to Phosphorus Nutrition Education for the Adolescent Kidney Patient.

Transfer of microRNA-486-5p from human endothelial colony forming cell–derived exosomes reduces ischemic kidney injury

Administration of human cord blood endothelial colony-forming cells (ECFCs) or their exosomes protects mice against kidney ischemia/reperfusion injury. Here we studied the microRNA (miRNA) content of ECFC exosomes and the role of miRNA transfer in kidney and endothelial cell protection. ECFC exosomes were enriched in miR-486-5p, which targets the phosphatase and tensin homolog (PTEN) and the Akt pathway. In cultured endothelial cells exposed to hypoxia, incubation with ECFC exosomes increased miR-486-5p, decreased PTEN, and stimulated Aktphosphorylation. Exposure of hypoxic endothelial cellsto conditioned medium from ECFCs pretreated with anti-miR-486-5p blocked increases in miR-486-5p and phosphorylated Akt, restored expression of PTEN, and enhanced apoptosis. Coculture of endothelial cells with ECFCs enhanced endothelial miR-486-5p levels. Targeting of PTEN by miR-486-5p was observed in endothelial cells, and PTEN knockdown blocked apoptosis. In mice with ischemic kidney injury, infusion of ECFC exosomes induced potent functional and histologic protection, associated with increased kidney miR-486-5p levels, decreased PTEN, and activation of Akt. Infusion of exosomes from ECFCs transfected with anti-miR-486-5p had no protective effect. Thus, delivery of ECFC exosomes reduces ischemic kidney injury via transfer of miR-486-5p targeting PTEN. Exosomes enriched in miR-486-5p could represent a therapeutic tool in acute kidney injury.

The Long-Term Follow-up and Support for Living Organ Donors: A Center-Based Initiative Founded on Developing a Community of Living Donors.

Transplant professionals recognize that the long-term follow-up of living organ donors is a priority, yet there has been no implemented solution to this problem. This critical gap is essential, because the transplant field is now emphasizing living donation as a means to address the organ shortage. We detail our living donor initiative, which sets several priorities we recognize as fundamental to persons who have donated organs at our transplant center. This intervention attempts to mitigate the donor and center factors that are known to contribute to the lack of long-term follow-up. Beyond that, our goals are aimed at providing ongoing engagement, wellness, clinical data accrual, laboratory follow-up, and social support for our living donors, in continuity. Our ultimate goal is to nurture the development of local living donor community networks by providing social engagement for current and past donors, which also serves as a platform for greater population education on the societal importance of living donation. This initiative is based on joint recognition by our transplant team and our hospital leadership that supporting the long-term welfare of living donors is essential to accomplishing the goal of expanding living donor transplantation. The transplant team and hospital missions are aligned, and both contribute resources to the initiative.

“What’s the Risk?” Assessing and Mitigating Risk in Cardiothoracic Surgery

“What’s the Risk?” Assessing and Mitigating Risk in Cardiothoracic Surgery

AIUM Practice Parameter for the Performance of Ultrasound Vascular Mapping for Preoperative Planning of Dialysis Access

AIUM Practice Parameter for the Performance of Ultrasound Vascular Mapping for Preoperative Planning of Dialysis Access

Worldwide growing epidemic of CKD: fact or fiction?

Chronic kidney disease (CKD) is recognized as a major noncommunicable disease of growing epidemic dimension worldwide. However, recent surveys have shown a marked heterogeneity of CKD prevalence in the general population, from ∼5% to 13% across countries. Methodological issues, genetic diversity, and dietary factors may all play a role. An important, currently emerging aspect of CKD epidemiology is the variability of CKD trends over time, with some countries showing a stable or even a decreased prevalence.

Failure of Calcineurin Inhibitor (Tacrolimus) Weaning Randomized Trial in Long-Term Stable Kidney Transplant Recipients.

Long-term renal transplant outcome is limited by side effects of immunosuppressive drugs, particularly calcineurin inhibitor (CNI). We assumed that some patients selected for a "low immunological risk of rejection" could be eligible and benefit from a CNI weaning strategy. We designed a prospective, randomized, multicenter, double-blind placebo-controlled clinical study (Eudract: 2010-019574-33) to analyze the benefit-risk ratio of tacrolimus weaning on highly selected patients (≥4 years of transplantation, normal histology, stable graft function, no anti-HLA immunization). The primary endpoint was improvement of renal function. Fifty-two patients were scheduled in each treatment arm, placebo compared to the CNI maintenance arm. Only 10 patients were eligible and randomized. Five patients were assigned to the placebo arm and five were assigned to the tacrolimus maintenance arm. In the tacrolimus maintenance arm, all patients maintained stable graft function and no immunological events occurred. Contrastingly, in the placebo arm, all five patients had to reintroduce a full dose of tacrolimus since three of them presented an acute rejection episode (one humoral, one mixed, and one borderline) and two displayed anti-HLA antibodies without histological lesion (one donor-specific antibodies [DSA] and one non-DSA). Clearly, tacrolimus withdrawal must be avoided even in long-term highly selective stable kidney recipients.

61 Nicotinamide ameliorates PE and FGR in a mouse model of PE

Introduction We have reported that lack of eNOS exacerbated preeclampsia (PE) via activation of endothelin (ET) system (Li, Takahashi et al. J Am Soc Nephrol, 2012). But inhibiting ET system is teratogenic, and is not suitable for pregnant women. Nicotinamide, a non-taratogenic vitamin, inhibits ADP ribosyl cyclase and relaxes vasculatures preconstricted with ET-1. Objectives The purpose of this study is to clarify whether nicotinamide is useful for treating or preventing PE and fetal growth restriction (FGR) associated with it. Methods Recombinant adenovirus to overproduce sFlt-1 was administered to ICR mice on 14.5 dpc to make a PE model. Changes in maternal body weight and BP were monitored. Dams were sacrificed on 18.5 dpc for further analysis. Results BP of the PE mice was significantly increased, PE dams miscarried, and fetal body weights were significantly decreased. Nicotinamide decreased BP of the dams by inhibiting ADP ribosyl cyclase, and prolonged pregnancy. Acting via NAD salvage pathway, nicotinamide normalized fetal ATP synthesis and prevented FGR. Conclusions Because nicotinamide benefits both mothers and pups, it merits evaluation for preventing and treating PE and FGR associated with it in humans.