Monogenic Etiology of Hypertension.

Monogenic hypertension encompasses a group of conditions wherein single gene mutations result in increased renal sodium reabsorption manifesting as low renin hypertension. As these diseases are rare, their contribution to hypertension in children and adolescents is often overlooked. Precise diagnosis is essential in those who have not been found to have more common identifiable causes of hypertension in adolescents, since treatment strategies for these rare conditions are specific and different from antihypertensive regimens for the other more common causes of hypertension in this age group.

Primary Causes of Hypertensive Crisis.

Hypertensive crisis, especially in children, is a rare condition and is defined as a sudden and abrupt elevation in blood pressure that poses a threat of rapid onset of end-organ damage. Symptomatic hypertension requires urgent and thorough evaluation and management. In most patients with hypertensive crisis, a specific cause can be found with targeted investigation.

Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs.

MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls.

Successful Application of Whole Genome Sequencing in a Medical Genetics Clinic.

A pilot program was initiated using whole genome sequencing (WGS) to diagnose suspected genetic disorders in the Genetics Clinic at Children's Hospital of Wisconsin. Twenty-two patients underwent WGS between 2010 and 2013. Initially, we obtained a 14% (3/22) diagnosis rate over 2 years; with subsequent reanalysis, this increased to 36% (8/22).

Complete resolution of trichodysplasia spinulosa in a pediatric renal transplant patient: Case report and literature review.

TS of immunosuppression is a rare, disfiguring dermatologic condition caused by TS-associated polyomavirus in immunosuppressed patients. It is difficult to treat, with no clearly described approach to resolve the condition completely and safely. We report a child with a renal transplant who developed TS and was treated with significant reduction in immunosuppression and transient use of cidofovir cream.

Heat shock proteins in the kidney.

Heat shock proteins (Hsps) are essential to cell survival through their function as protein chaperones. The role they play in kidney health and disease is varied. Hsp induction may be either beneficial or detrimental to the kidney, depending on the specific Hsp, type of cell, and context.

Mice with an absent stress response are protected against ischemic renal injury.

Inducible heat shock proteins (HSPs), regulated by heat shock factor-1 (HSF-1), protect against renal cell injury in vitro. To determine whether HSPs ameliorate ischemic renal injury in vivo, HSF-1 functional knockout mice (HSF-KO) were compared with wild-type mice following bilateral ischemic renal injury. Following injury, the kidneys of wild-type mice had the expected induction of HSP70 and HSP25; a response absent in the kidneys of HSF-KO mice.

Donor and recipient BKV-specific IgG antibody and posttransplantation BKV infection: a prospective single-center study.

Background: The study evaluated the relationship of pretransplantation BK virus (BKV)-specific donor and recipient serostatus to posttransplantation BKV infection.

Methods: Two hundred forty adult de novo kidney-only recipients and 15 pediatric recipients were prospectively enrolled and followed for a minimum of 18 months. Pretransplantation BKV serostatus was available for 192 adult and 11 pediatric donor-recipient pairs.

Chromosome substitution modulates resistance to ischemia reperfusion injury in Brown Norway rats.

Brown Norway rats (BN, BN/NHsdMcwi) are profoundly resistant to developing acute kidney injury (AKI) following ischemia reperfusion. To help define the genetic basis for this resistance, we used consomic rats, in which individual chromosomes from BN rats were placed into the genetic background of Dahl SS rats (SS, SS/JrHsdMcwi) to determine which chromosomes contain alleles contributing to protection from AKI. The parental strains had dramatically different sensitivity to ischemia reperfusion with plasma creatinine levels following 45 min of ischemia and 24 h reperfusion of 4.

Renal function and proteinuria after successful immunosuppressive therapies in patients with FSGS.

Background And Objectives: In the FSGS Clinical Trial, 22 cyclosporine-treated and 20 mycophenolate/dexamethasone-treated patients experienced a complete or partial remission after 26 weeks, completed 52 weeks of treatment, and were studied through 78 weeks. Herein, changes in the urine protein/creatinine ratio (UP/C) and estimated GFR (eGFR) throughout the entire study period are defined.

Design, Setting, Participants, And Measurements: The FSGS Clinical Trial, which was conducted from November 2004 to January 2010, enrolled patients aged 2-40 years, with eGFR ≥40 ml/min per 1.

Protective effect of 20-HETE analogues in experimental renal ischemia reperfusion injury.

While it is known that the arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to ischemic injury in the heart and brain, its role in kidney injury is unclear. Here we determined the effects on ischemia-reperfusion injury of the 20-HETE analogues, 20-hydroxyeicosa-5(Z), 14(Z)-dienoic acid (5,14-20-HEDE), and N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine (5,14-20-HEDGE), and of the inhibitor of 20-HETE synthesis N-hydroxy-N-(4-butyl-2 methylphenyl) formamidine (HET0016). Using Sprague-Dawley rats we found that while treatment with the inhibitor exacerbated renal injury, infusion of both 5,14-20-HEDE and 5,14-20-HEDGE significantly attenuated injury when compared to vehicle or inhibitor-treated rats.

Oxidant-mediated apoptosis in proximal tubular epithelial cells following ATP depletion and recovery.

Oxidant-mediated apoptosis has been implicated in renal injury due to ischemia reperfusion (IR); however, the apoptotic signaling pathways following IR have been incompletely defined. The purpose of this study was to examine the role of oxidants on cell death in a model of in vitro simulated IR injury in renal proximal tubular epithelial cells by analyzing the effects of a cell-permeable superoxide dismutase mimetic, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTmPyP). Renal proximal tubular epithelial cells were ATP depleted for 2, 4, or 6 h, followed by 2 h of recovery.

Favorable balance of anti-oxidant/pro-oxidant systems and ablated oxidative stress in Brown Norway rats in renal ischemia-reperfusion injury.

Oxidative stress is important in the pathogenesis of renal ischemia-reperfusion (IR) injury; however whether imbalances in reactive oxygen production and disposal account for susceptibility to injury is unclear. The purpose of this study was to compare necrosis, apoptosis, and oxidative stress in IR-resistant Brown Norway rats vs. IR-susceptible Sprague-Dawley (SD) rats in an in vivo model of renal IR injury.

Resistance to ischemic acute renal failure in the Brown Norway rat: a new model to study cytoprotection.

Background: An in vivo model of intrinsic resistance to ischemia could be invaluable to define how specific pathways to injury or putative protectors from injury affect the severity of acute renal failure (ARF). The purpose of this study was to determine whether separate rat strains had differential sensitivity to renal ischemia, characterize the extent of protection, and begin to define differences in gene expression that might impact on the severity of ARF.

Methods: The sensitivity to 45 minutes of renal ischemia in Sprague-Dawley rat (SD) was compared with 2 lines of Brown-Norway rats (BN/Mcw, BN/Hsd).

Prevention of acute ischemic renal failure by targeted delivery of growth factors to the proximal tubule in transgenic mice: the efficacy of parathyroid hormone-related protein and hepatocyte growth factor.

Treatment of acute renal failure (ARF) would be enhanced by identification of factors that accelerate renal recovery from injury. Parathyroid hormone-related protein (PTHrP) and hepatocyte growth factor (HGF) have been shown to stimulate proliferation in proximal nephron-derived cells. For studying the pathophysiologic roles and therapeutic potential of these two factors in ARF, transgenic mice overexpressing PTHrP or HGF in the proximal tubule under the direction of the gamma-glutamyl transpeptidase-I promoter were developed.

Urinary heat shock protein-72 excretion in clinical and experimental renal ischemia.

Renal ischemia not only causes injury but also induces repair mechanisms, such as the cellular induction of the 72-kilodalton heat shock protein HSP-72. The aim of this study was to determine whether HSP-72 is excreted in urine after ischemic renal injury. The first urine of six pediatric allograft recipients was examined for proteinuria and urinary HSP-72 excretion.

Hsp27 associates with actin and limits injury in energy depleted renal epithelia.

The purpose of the study was to determine whether Hsp27 interacts with actin and could protect against selected manifestations of injury from energy depletion in renal epithelia. LLC-PK1 cells were stably transfected to overexpress human Hsp27 tagged with green fluorescence protein (GFP). Transfected expression of the labeled Hsp27 did not reduce endogenous Hsp25 levels in the cells compared with either nontransfected cells or cells transfected with GFP alone used as the transfectant control (G).

Functional activation of heat shock factor and hypoxia-inducible factor in the kidney.

Renal ischemia is the result of a complex series of events, including decreases in oxygen supply (hypoxia) and the availability of cellular energy (ATP depletion). In this study, the functional activation of two stress-responsive transcription factors, i.e.

Ischemic conditioning prevents Na,K-ATPase dissociation from the cytoskeletal cellular fraction after repeat renal ischemia in rats.

Recent studies have suggested that heat shock proteins (HSPs) are involved in the restoration of the cytoskeletal anchorage of Na,K-ATPase after renal ischemia. To determine their role in ischemic conditioning, we investigated whether cytoskeletal Na,K-ATPase was stabilized during repeat ischemia concurrent with 25-kD and 70-kD HSPs induction. Anesthetized rats either underwent single unilateral renal ischemia or were conditioned with bilateral renal ischemia and, after 18 h of reflow, were then subjected to repeat unilateral renal ischemia.

Pneumothoraces complicating systemic lupus erythematosus with nephritis.

Pneumothorax is an infrequently reported complication of systemic lupus erythematosus (SLE) and carries with it a grave prognosis. We report a patient with SLE and nephritis who developed pneumothorax that responded to aggressive and prolonged therapy. Surgical management with prolonged evacuation, judicious immunosuppression, and aggressive diagnosis and treatment of infection can improve the outcome for these patients.