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The anion gap (AG) is a mathematical construct that compares the blood sodium concentration with the sum of the chloride and bicarbonate concentrations. It is a helpful calculation that divides the metabolic acidoses into 2 categories: high AG metabolic acidosis (HAGMA) and hyperchloremic metabolic acidosis-and thereby delimits the potential etiologies of the disorder. When the [AG] is compared with changes in the bicarbonate concentration, other occult acid-base disorders can be identified. Furthermore, finding that the AG is very small or negative can suggest several occult clinical disorders or raise the possibility of electrolyte measurement artifacts. In this installment of AJKD's Core Curriculum in Nephrology, we discuss cases that represent several very common and several rare causes of HAGMA. These case scenarios highlight how the AG can provide vital clues that direct the clinician toward the correct diagnosis. We also show how to calculate and, if necessary, correct the AG for hypoalbuminemia and severe hyperglycemia. Plasma osmolality and osmolal gap calculations are described and when used together with the AG guide appropriate clinical decision making.

A Woman with Nausea, Diarrhea, and Acute Kidney Failure A 76-year-old woman with a history of type 2 diabetes, obstructive sleep apnea, coronary artery disease, and heart failure with reduced eject...

We describe two patients who presented with severe autoimmune hemolytic anemia in the setting of babesiosis. Notably, one patient was immunocompetent but was found to have splenic infarcts of uncertain duration, while the other patient developed disease in the context of asplenia secondary to prior surgical removal of the spleen. Both patients received antibiotics and transfusion support and eventually made a full recovery. While the patient in case 1 had parasitemia >10%, neither patient ultimately required therapeutic red blood cell exchange transfusion during the course of their respective hospitalizations. Our two cases emphasize the importance of recognizing the hemolytic anemia component of this potentially life-threatening infection, and the importance of rapidly initiating treatment in these complex clinical situations.

Erythropoietin-stimulating agents (ESA) have revolutionized the management of anemia. However, these agents are not always utilized with proper monitoring parameters, which can present significant safety concerns, unwarranted drug expenditures, and decreased ESA efficacy. This retrospective study assessed the utilization of all ESAs in non–intensive care unit hospitalized patients at a large academic medical center from August 18, 2018, to August 31, 2018, using established guideline-based assessment criteria. Among the 167 doses of ESA evaluated, 86% (n = 144) were utilized in accordance with guideline-based assessment criteria regarding laboratory monitoring of iron studies. However, 24% (n = 40) of ESA doses were administered to patients with active, untreated iron deficiency at the time of administration. Although most ESA doses were utilized in accordance with the guideline-based criteria, interventions can be implemented to further improve anemia treatment. Implementing a protocol-driven anemia management service is one strategy that can improve patient care, advance patient safety, and be cost-beneficial.

We describe a 68-year-old man who presented with progressive weakness in proximal muscles of all four limbs and was found to have autoantibody-negative necrotizing autoimmune myopathy (NAM). His myopathy was refractory to corticosteroids and methotrexate, but subsequently demonstrated successful response to intravenous immunoglobulin (IVIG). The patient also received rituximab, but the timing of his recovery favored IVIG as the more important factor in terms of efficacy. Treatment guidelines for seronegative necrotizing myopathies are lacking. This case suggests a potential efficacious treatment option for the seronegative subset of NAM.

The objective of this study was to evaluate the safety and efficacy of apixaban 5 mg twice daily vs 2.5 mg twice daily for nonvalvular atrial fibrillation or venous thromboembolism in patients with chronic kidney disease stage 4 and 5, including those on hemodialysis. Data were collected retrospectively on patients with advanced chronic kidney disease and nonvalvular atrial fibrillation and/or venous thromboembolism who received apixaban while hospitalized at our institution between January 2013 and August 2018. The 5 mg twice daily group included 22 patients, and the 2.5 mg twice daily group included 73 patients. There was no difference between groups in major bleeding events (9.1% vs. 12.3%, P = 1.00), any bleeding event (45.4% vs. 67.1%, P = 0.08), ischemic stroke (0% vs. 2.7%, P = 1.00), or venous thromboembolism (4.5% vs. 0%, P = 0.23). Subgroup analyses of patients with a serum creatinine >2.5 mg/dL or creatinine clearance

Background Hydroxychloroquine (HCQ) poisoning is a life-threatening but treatable toxic ingestion. The scale of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) and the controversial suggestion that HCQ is a treatment option have led to a significant increase in HCQ use.1 Hence, HCQ poisoning should be at the top-of-mind for emergency providers in cases of toxic ingestion. Treatment for HCQ poisoning includes sodium bicarbonate, epinephrine, and aggressive electrolyte repletion.2–5 Here, we highlight the use of hypertonic saline and diazepam. Case Report We describe the case of a 37-year-old man who presented to the emergency department (ED) after the ingestion of approximately 16 grams of HCQ tablets (initial serum concentration 4,270 ng/mL). He was treated with an epinephrine infusion, hypertonic sodium chloride, high-dose diazepam, sodium bicarbonate, and aggressive potassium repletion. Persistent altered mental status necessitated intubation, and he was managed in the medical intensive care unit until his QRS widening and QTc prolongation resolved. After his mental status improved and it was confirmed that his ingestion was not with the intent to self-harm, he was discharged home with outpatient follow-up. Why should an emergency physician be aware of this? For patients presenting with HCQ overdose and an unknown initial serum potassium level, high-dose diazepam and hypertonic sodium chloride should be started immediately for the patient with widened QRS. The choice of hypertonic sodium chloride instead of sodium bicarbonate is to avoid exacerbating underlying hypokalemia which may in turn potentiate unstable dysrhythmia. In addition, early intubation should be a priority in vomiting patients as both HCQ toxicity and high-dose diazepam cause profound sedation.

A man in his 50s with dialysis-dependent end-stage renal disease, several weeks history of progressive skin bruising and acute-onset gastrointestinal bleeding presented to the emergency department following a syncopal event during routine haemodialysis owing to profound hypotension. He was found to have a severe normocytic, normochromic anaemia requiring several blood transfusions. He followed a diet lacking fruits and vegetables and stopped taking renal multivitamins. All parameters of coagulation were unremarkable, but serum vitamin C level was undetectable, supporting a diagnosis of scurvy. Although typically associated with individuals who are at risk of malnourishment, such as those with alcohol use disorder, malabsorption, and those who experience homelessness, scurvy should be considered in patients receiving renal replacement therapy as vitamin C is removed during haemodialysis.

A Man with Facial Droop, Dysarthria, and Kidney Failure A 37-year-old man with a history of injection-drug use presented with a facial droop, dysarthria, and kidney failure. The creatinine level wa...

Topiramate is an anticonvulsant that is being increasingly used for a number of different off-label indications. Its inhibition of carbonic anhydrase isoenzymes can lead to metabolic acidosis, elevated urine pH, reduced urine citrate, and hypercalciuria, thereby creating a milieu that is ripe for calcium phosphate stone formation. In this review, we describe a case of topiramate-induced metabolic acidosis. We review the frequency of metabolic acidosis among children and adults, as well as the mechanism of hyperchloremic metabolic acidosis and renal tubular acidosis in topiramate users. Finally, we describe the long-term effects of topiramate-induced metabolic acidosis, including nephrolithiasis, nephrocalcinosis, and bone degradation. Patients who are prescribed topiramate should be carefully monitored for metabolic derangements, and they may benefit from alkali supplementation, or in extreme cases, discontinuation of the drug altogether.

Primary mitochondrial diseases (MD) are complex, heterogeneous inherited diseases caused by mutations in either the mitochondrial or nuclear DNA. Glomerular diseases in MD have been reported with tRNA mutation m.3243A>G causing a syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). We describe here a case of focal segmental glomerulosclerosis (FSGS) associated with a new tRNA mutation site. A 34-year-old man with a history of living related kidney transplantation, diabetes, hearing loss, and developmental delay presented to the outpatient clinic with complaints of new behavioral difficulties, worsening symptoms, and brain involvement on imaging. Physical examination was remarkable for difficulty hearing, a pattern of dysarthric speech, and cerebellar gait. Laboratory investigations including lactate levels were unremarkable. Based on this set of clinical circumstances, concern for an underlying genetic abnormality was raised. Multiple metabolic tests were unremarkable. Whole exome sequencing revealed a mitochondrial MT-TW tRNA change at position m.5538G>A. Genotype-phenotype correlations are consistent with this tRNA mutation as a cause of his symptoms. To the best of our knowledge, this is the first case describing FSGS-associated MD caused by an m.5538 G>A mutation. Consideration of an underlying MD should be made in patients presenting with deafness, neurologic changes, diabetes, and renal failure.

Hypomagnesemia is common among hospitalized patients, particularly those who are critically ill. It can be associated with a number of potentially life-threatening cardiovascular, neurological and behavioral manifestations. As opposed to acute, chronic hypomagnesemia is often underdiagnosed and underreported and as such may pose a diagnostic and therapeutic problem.We describe a case of magnesium wasting in a middle-aged woman with head and neck cancer who presented with recurrent syncopal episodes complicated by a femur fracture 4 months after completing a course of carboplatin-containing chemotherapy. Fractional excretion of magnesium of 16% was consistent with renal wasting of magnesium. After ruling out all common causes of hypomagnesemia, it was concluded that she sustained carboplatin-induced renal tubular damage making her relatively resistant to magnesium supplementation.Several antineoplastic agents have been linked to chronic hypomagnesemia including anti-epidermal growth factor receptor agents such as cetuximab and panitumumab, cyclosporine, and the platinum-based agents cisplatin and carboplatin. The example case presented here illustrates the importance of chronic hypomagnesemia and its possible debilitating effects following carboplatin-containing chemotherapy. A growing numbers of cancer survivors are treated with these antineoplastic agents, and are hospitalized for non-cancer-related problems. These patients may have prolonged hypomagnesemia, and hence pose a diagnostic dilemma. We review the pathophysiology, etiology, diagnosis, clinical manifestations, monitoring and treatment of hypomagnesemia, with special attention to mechanisms of renal damage caused by platinum-containing chemotherapeutic agents.

A Man with Alcohol Withdrawal and Altered Mental Status A 54-year-old man was admitted to the hospital for alcohol withdrawal. On the fifth day, after resolution of withdrawal symptoms, he was foun...

We present the case of a 47-year-old man with a history of diabetes mellitus and diabetic nephropathy who was admitted to our hospital with acute uremic myopericarditis. Echocardiography demonstrated a fibrinous pericardial effusion. The patient was initiated on hemodialysis for hyperkalemia, metabolic acidosis, and uremia. He subsequently developed shock from cardiac tamponade, which required emergent pericardiocentesis. He was notably without tachycardia while he was hypotensive, and his admission electrocardiogram did not show typical ST- or PR-segment changes typically associated with acute pericarditis. This case highlights important differences between uremic pericarditis and other prevalent types of acute pericarditis, including the lack of tachycardia during tamponade and normal electrocardiography. Uremic pericarditis is now a less common diagnosis. It is often seen in the setting of previously undiagnosed advanced kidney disease or when patients are ineffectively dialyzed. Given its atypical features, low incidence, and adverse attendant complications, internists must maintain a high degree of suspicion to correctly diagnose acute uremic pericarditis.

A 32-year-old man was admitted to this hospital after being found in an unresponsive state in his jail cell. He had jaundice and encephalopathy; results of liver-function tests were abnormal, and CT revealed cerebral edema. Diagnostic tests were performed.

There are a significant number of dermatoses associated with renal abnormalities and disease, and dermatologists need to be keenly aware of their presence in order to avoid overlooking important skin conditions with potentially devastating renal complications. This review discusses important nephrocutaneous disease associations and recommendations for the appropriate urgency of referral to nephrology colleagues for diagnosis, surveillance, and early management of potential renal sequelae. Part II of this 2-part continuing medical education article addresses inflammatory and medication-related nephrocutaneous associations.

There are a significant number of diseases and treatment considerations of considerable importance relating to the skin and renal systems. This emphasizes the need for dermatologists in practice or in clinical training to be aware of these associations. Part I of this 2-part continuing medical education article reviews the genetic syndromes with both renal and cutaneous involvement that are most important for the dermatologist to be able to identify, manage, and appropriately refer to nephrology colleagues. Part II reviews the inflammatory syndromes with relevant renal manifestations and therapeutic agents commonly used by dermatologists that have drug-induced effects on or require close consideration of renal function. In addition, we will likewise review therapeutic agents commonly used by nephrologists that have drug-induced effects on the skin that dermatologists are likely to encounter in clinical practice. In both parts of this continuing medical education article, we discuss diagnosis, management, and appropriate referral to our nephrology colleagues in the context of each nephrocutaneous association. There are a significant number of dermatoses associated with renal abnormalities and disease, emphasizing the need for dermatologists to be keenly aware of their presence in order to avoid overlooking important skin conditions with potentially devastating renal complications. This review discusses important nephrocutaneous disease associations with recommendations for the appropriate urgency of referral to nephrology colleagues for diagnosis, surveillance, and early management of potential renal sequelae.

In many states undocumented immigrants with end stage renal disease (ESRD) do not have access to regular, thrice weekly dialysis. The term "compassionate dialysis" is used to describe dialysis that is provided on an emergent basis, when patients are in extremis from symptoms of volume overload or suffer from life-threatening electrolyte abnormalities. In this editorial, one particularly poignant anecdote is presented from the experience of one of the authors (AZF) as a nephrologist in Texas, a state where undocumented immigrants have faced difficulties in accessing regular dialysis. We then describe the legislation that allows the right to regular dialysis to be determined on a state by state basis. We offer some potential solutions to this challenging issue, and we describe the difficulties that lay ahead given the uncertain future of the Affordable Care Act.

Neurologic complications are common after solid-organ transplantation, occurring in one-third of patients. Immunosuppression-related neurotoxicity (involving calcineurin inhibitors and corticosteroids), opportunistic central nervous system infections, seizures, and delirium are some of the causes of neurologic symptoms following solid-organ transplantation. An uncommon often missed complication posttransplantation involves buildup of ammonia levels that can lead to rapid clinical deterioration even when treated. Ammonia levels are not routinely checked due to the myriad of other explanations for encephalopathy in a transplant recipient. A treatment of choice for severe hyperammonemia involves renal replacement therapy (RRT), but there are no guidelines on the mode or parameters of RRT for reducing ammonia levels. Hyperammonemia in a transplant recipient poses specific challenges beyond the actual condition because the treatment (RRT) involves significant hemodynamic fluctuations that may affect the graft. In this review, we describe a patient with posttransplantation hyperammonemia and discuss the pathways of ammonia metabolism, potential factors underlying the development of hyperammonemia posttransplantation, and choice of appropriate therapeutic options in these patients.

A Man with Acute Renal Failure and Hematuria A 71-year-old man presented with acute renal failure and hematuria. Examination of the urinary sediment revealed numerous nondysmorphic red cells, a few...

A Woman with Hypertension, Fatigue, and Altered Mental Status A 45-year-old woman presented with hypertension, fatigue, and episodic confusion. After medications were administered, the blood pressu...

Hypertension in renal transplant recipients is common and ranges from 50% to 80% in adult recipients and from 47% to 82% in pediatric recipients. Cardiovascular morbidity and mortality and shortened allograft survival are important consequences of inadequate control of hypertension. In this review, we examine the epidemiology, pathophysiology, and management considerations of post-transplant hypertension. Donor and recipient factors, acute and chronic allograft injury, and immunosuppressive medications may each explain some of the pathophysiology of post-transplant hypertension. As observed in other patient cohorts, renal artery stenosis and adrenal causes of hypertension may be important contributing factors. Notably, BP treatment goals for renal transplant recipients remain an enigma because there are no adequate randomized controlled trials to support a benefit from targeting lower BP levels on graft and patient survival. The potential for drug-drug interactions and altered pharmacokinetics and pharmacodynamics of the different antihypertensive medications need to be carefully considered. To date, no specific antihypertensive medications have been shown to be more effective than others at improving either patient or graft survival. Identifying the underlying pathophysiology and subsequent individualization of treatment goals are important for improving long-term patient and graft outcomes in these patients.

Objective Hyperammonemic encephalopathy is an uncommon but severe complication of the Roux-en-Y gastric bypass surgery for obesity. Mechanisms underlying this complication are incompletely understood, resulting in delayed recognition and management. This study evaluated common laboratory findings and possible etiology of hyperammonemic encephalopathy after successful Roux-en-Y gastric bypass surgery. Methods A retrospective review of 20 patients identified through our own clinical practice was conducted, with the addition of similar cases from other institutions identified through the review of literature. Results Patients presenting with hyperammonemic encephalopathy after Roux-en-Y gastric bypass surgery presented with overlapping clinical and laboratory findings. Common features included: (1) weight loss following successful Roux-en-Y gastric bypass for obesity; (2) hyperammonemic encephalopathy accompanied by elevated plasma glutamine levels; (3) absence of cirrhosis; (4) hypoalbuminemia; and (5) low plasma zinc levels. The mortality rate was 50%. Ninety-five percent of patients were women. Three patients were diagnosed with proximal urea cycle disorders. One patient experienced improvement in the hyperammonemia after surgical correction of spontaneous splenorenal shunt. Conclusions Hyperammonemic encephalopathy after Roux-en-Y gastric bypass surgery is a newly recognized, potentially fatal syndrome with diverse pathophysiologic mechanisms encompassing genetic and nongenetic causes.

We describe a 71-year-old man who presented with abdominal pain, lower-extremity edema, recent unintentional weight loss, hypertension, hyperglycemia, hypokalemia, and metabolic alkalosis. Serum cortisol levels remained elevated after overnight high-dose dexamethasone suppression. Magnetic resonance imaging revealed a small mass in the head of the pancreas with scattered liver metastases. Both endoscopic ultrasound-guided pancreatic biopsy and liver biopsy revealed a well-differentiated neuroendocrine tumor. These lesions did not show significant uptake on octreotide scan. Medical management and hepatic artery chemoembolization were attempted. Ultimately, the patient underwent bilateral adrenalectomy, but died within 4 months of symptom onset secondary to postoperative complications.

Background Half of surgically created arteriovenous fistulas (AVFs) require additional intervention to effectively support hemodialysis. Postoperative care and complications may affect clinical maturation. Study Design Hemodialysis Fistula Maturation (HFM) Study, a 7-center prospective cohort study. Setting & Participants 491 patients with single-stage AVFs who had neither thrombosis nor AVF intervention before a 6-week postoperative ultrasonographic examination and who required maintenance hemodialysis. Predictors Postoperative care processes and complications. Outcomes Attempted cannulation, successful cannulation, and unassisted and overall clinical maturation as defined by the HFM Study criteria. Results AVF cannulation was attempted in 443 of 491 (90.2%) participants and was eventually successful in 430 of these 443 (97.1%) participants. 263 of these 430 (61.2%) reached unassisted and 118 (27.4%) reached assisted AVF maturation (overall maturation, 381/430 [88.6%]). Attempted cannulation was less likely in patients of surgeons with policies for routine 2-week versus later-than-2-week first postoperative visits (OR, 0.21; 95% CI, 0.06-0.70), routine second postoperative follow-up visits (OR, 0.39; 95% CI, 0.15-0.97), and a routine clinical postoperative ultrasound (OR, 0.28; 95% CI, 0.14-0.55). Attempted cannulation was also less likely among patients undergoing procedures to assist maturation (OR, 0.51; 95% CI, 0.27-0.98). Unassisted maturation was more likely for patients treated in facilities with access coordinators (OR, 1.91; 95% CI, 1.17-3.12), but less likely after precannulation nonstudy ultrasounds (OR per ultrasound, 0.42 [95% CI, 0.26-0.68]) and initial unsuccessful cannulation attempts (OR per each additional attempt, 0.90 [95% CI, 0.83-0.98]). Overall maturation was less likely with infiltration before successful cannulation (OR, 0.44; 95% CI, 0.22-0.89). Among participants receiving maintenance hemodialysis before AVF surgery, unassisted and overall maturation were less likely with longer intervals from surgery to initial cannulation (ORs for each additional month of 0.81 [95% CI, 0.76-0.88] and 0.93 [95% CI, 0.89-0.98], respectively) and from initial to successful cannulation (ORs for each additional week of 0.87 [95% CI, 0.81-0.94] and 0.88 [95% CI, 0.83-0.94], respectively). Limitations Surgeons' management policies were assessed only by questionnaire at study onset. Most participants received upper-arm AVFs, planned 2-stage AVFs were excluded, and maturation time windows were imposed. Some care processes may have been missed and the observational design limits causal attribution. Conclusions Multiple processes of care and complications are associated with AVF maturation outcomes.

Worldwide, there have been

The prevalence of hypertension in the general population has steadily climbed over the past several decades and hypertension is a primary or secondary diagnosis in nearly a fourth of hospitalized adults. Hospitalization is often a time of pertubation in a patient's usual blood pressure control, with pain, anxiety and missed medications all risk factors for severe hypertension. Hospitalists are often faced with severe hypertension in a patient not previously known to them and this presents a challenge of how best to assess the clinical importance of blood pressure elevation. An additional challenge is the lack of literature to guide the optimal management of hypertension in inpatients. This review aims to describe the scope of the problem, to describe the near and long-term risks of overzealous blood pressure management, and to identify areas for future study.

(2017). Calcinosis Cutis and Renal Disease: An Evolving Story. Baylor University Medical Center Proceedings: Vol. 30, No. 3, pp. 370-371.

Hydroxocobalamin is a recently approved antidote for the treatment of cyanide poisoning. The case presented involves a young patient administered empiric hydroxocobalamin due to suspected cyanide overdose. Due to the development of acute kidney injury and severe metabolic derangement, emergent hemodialysis was initiated. Unfortunately, hemodialysis was confounded by a recurrent “blood leak” alarm. This unforeseen effect was secondary to interference from hydroxocobalamin. Hydroxocobalamin causes orange/red discoloration of bodily fluids and permeates the dialysate. This leads to defraction of light in the effluent path of the blood leak detector from discolored dialysate, which can result in activation of the blood leak alarm and an inability to continue hemodialysis treatment. This case highlights several new and emerging critical concerns with this medication, including the potential consequence of delayed initiation of emergent renal replacement therapy with empiric administration, the need for increased awareness among clinicians of various disciplines, and the need for multidisciplinary communication.

Acquired 5-oxoprolinemia is increasingly recognized as a cause of anion gap metabolic acidosis. It predominantly occurs in chronically ill, malnourished women with impaired renal function and chronic acetaminophen ingestion. Depletion of glutathione and cysteine stores leads to elevated 5-oxoproline levels. N-acetylcysteine, given its effect in repleting glutathione and cysteine stores, has been proposed as a potential treatment for 5-oxoprolinemia, though reports of its successful use are lacking. We present a case of 5-oxoproline metabolic acidosis that persisted despite discontinuation of acetaminophen. However, the acidosis rapidly resolved with N-acetylcysteine administration.

Methemoglobinemia is a rare cause of tissue hypoxia that can quickly become fatal without immediate recognition and prompt treatment. It refers to an increase in methemoglobin in the red blood cells, which can be due to genetic deficiency of the enzymes responsible for reducing hemoglobin or can develop after exposure to oxidizing agents or xenobiotics. Local anesthetics, particularly benzocaine, have long been implicated in the formation of methemoglobin. Benzocaine is used for teething pain as well as before invasive procedures such as intubation and transesophageal echocardiogram. In this case report, we describe a patient with acute appendicitis who developed severe methemoglobinemia following use of benzocaine during an emergent intubation. Our objective is to increase awareness of this rare but potentially fatal complication associated with the use of this anesthetic.

Renal artery stenosis and renovascular hypertension are important considerations in patients with hypertension that is difficult to control. The diagnosis may also have prognostic significance for progressive renal disease. The most common causes of renal artery stenosis are atherosclerotic disease and fibromuscular dysplasia. The pathophysiology of renal artery stenosis is reviewed, and the pros and cons of various imaging studies in the appropriate clinical setting are discussed. Treatment includes aggressive control of hypertension, dealing with associated cardiac risk factors, and angioplasty or surgery in specific circumstances.

Hypertension is very common in patients with chronic kidney disease (CKD); it causes early loss of kidney function and accelerated cardiovascular morbidity and mortality. African American patients with hypertension and genetic disposition are at an even higher risk for renal disease and ultimately renal failure. Hypertensive patients with CKD should aim for stringent blood pressure (BP) control (target < 130/80 mm Hg) requiring more than one drug with renin-angiotensin-aldosterone system blockade as a component of therapy targeting both hyper tension and proteinuria. Management of hypertension in the dialysis population should focus on ambulatory measurements of BP and the use of longer-acting antihypertensive drugs, with their dosage and timing adjusted according to their dialytic clearances. Hypertension is also common among kidney transplant recipients and contributes to graft loss and premature death. The target BP in transplant recipients is the same as in the CKD population, with no preference for one drug group over another. Unless contraindicated, angiotensin-converting enzyme inhibitors remain the drugs of choice for hypertension in patients with autosomal-dominant polycystic kidney disease, in whom diastolic cardiac dysfunction is a prominent feature.

Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity.We conducted a randomized, double-blind, placebo-controlled trial of extended-release dipyridamole, at a dose of 200 mg, and aspirin, at a dose of 25 mg, given twice daily after the placement of a new arteriovenous graft until the primary outcome, loss of primary unassisted patency (i.e., patency without thrombosis or requirement for intervention), was reached. Secondary outcomes were cumulative graft failure and death. Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates.At 13 centers in the United States, 649 patients were randomly assigned to receive dipyridamole plus aspirin (321 patients) or placebo (328 patients) over a period of 4.5 years, with 6 additional months of follow-up. The incidence of primary unassisted patency at 1 year was 23% (95% confidence interval [CI], 18 to 28) in the placebo group and 28% (95% CI, 23 to 34) in the dipyridamole-aspirin group, an absolute difference of 5 percentage points. Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P=0.03) and inhibited stenosis. The incidences of cumulative graft failure, death, the composite of graft failure or death, and serious adverse events (including bleeding) did not differ significantly between study groups.Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts. (ClinicalTrials.gov number, NCT00067119.)

Mucormycosis (zygomycosis) is an acute and often fatal opportunistic fungal infection. Predisposing factors in the development of mucormycosis are nonspecific and include hyperglycemia, hematologic malignancies, neutropenia, pharmacologic immunosuppression, solid organ or bone marrow/stem cell transplantation, burns, trauma, malnutrition, and intravenous drug use. Mucormycosis has also been described in patients with iron and aluminum overload, patients on dialysis, and patients receiving iron chelating therapy. We describe a 75-year-old man with myelodysplastic syndrome and iron overload secondary to multiple red blood cell transfusions who had been treated with deferoxamine chelation therapy. He was admitted to the hospital for atrial fibrillation, developed multiple organ failure, and died. Pulmonary invasive mucormycosis was demonstrated at autopsy. This case further documents an association between invasive mucormycosis, iron overload, and deferoxamine therapy.

A 28-year-old man with a history of inflammatory bowel disease (IBD) developed sudden-onset chest pain and dyspnea 9 days after esophagogastroduodenoscopy and colonoscopy. A chest radiograph demonstrated pneumomediastinum tracking along the left heart border. The spontaneous pneumomediastinum was presumed to be a complication of his severe colitis. The severity of our patient's symptoms ultimately necessitated a subtotal colectomy, a decision unrelated to the pneumomediastinum. IBD-associated pneumomediastinum can be attributed to retroperitoneal air leakage from severe colitis and usually resolves with conservative management.

There are a significant number of dermatoses associated with renal abnormalities and disease, and dermatologists need to be keenly aware of their presence in order to avoid overlooking important skin conditions with potentially devastating renal complications. This review discusses important nephrocutaneous disease associations and recommendations for the appropriate urgency of referral to nephrology colleagues for diagnosis, surveillance, and early management of potential renal sequelae. Part II of this 2-part continuing medical education article addresses inflammatory and medication-related nephrocutaneous associations.

The arteriovenous graft (AVG) is most often used in hemodialysis patients when an autogenous fistula is not feasible. The optimal location (forearm or upper arm) and configuration (loop or straight) of AVGs are not known. To evaluate relationships of AVG location and configuration with patency, we conducted a secondary analysis using data from a randomized, placebo-controlled trial of dipyridamole plus aspirin for newly placed AVG.Participants of the Dialysis Access Consortium (DAC) Graft Study with newly placed upper extremity prosthetic grafts involving the brachial artery were studied. Multivariable analyses adjusting for trial treatment group, center, gender, race, body mass index, diabetes, current treatment with chronic dialysis, and prior arteriovenous vascular access or central venous catheter were performed to compare outcomes of forearm (fAVG) and upper arm (uAVG) grafts, including loss of primary unassisted patency (LPUP) and cumulative primary graft failure (CGF). Subgroup analyses of graft configuration and outflow vein used were also conducted.A total of 508 of the 649 participants (78%) enrolled in the trial had an upper extremity brachial artery graft placed, 255 with fAVG and 253 with uAVG. Participants with fAVG were less often male (33% vs 43%; P = .03), African American (62% vs 78%; P .001), and receiving dialysis at the time of surgery (62% vs 80%; P .001). Participants with fAVG had a higher mean body mass index (33 vs 29; P .001). The LPUP (fAVG 70% vs uAVG 78%; P = .07) and CGF (33% vs 36%; P = .91) were similar between fAVG and uAVG at 1-year follow-up. In multivariable analysis, AVG location (uAVG vs fAVG) was not associated with LPUP (hazard ratio, 1.21; 95% confidence interval, 0.90-1.63; P = .20) or CGF (hazard ratio, 1.36; 95% confidence interval, 0.94-1.97; P = .10). LPUP did not differ significantly between fAVG and uAVG among subgroups based on AVG configuration (P = 1.00) or outflow vein used (P = .16).Patency was comparable between fAVG and uAVG despite the larger caliber veins often encountered in the upper arm in carefully selected patients. Our findings support the traditional view that, in order to preserve a maximal number of access sites, the forearm location should be considered first before resorting to an upper arm graft.

The endogenous organic acid metabolic acidoses that occur commonly in adults include lactic acidosis; ketoacidosis; acidosis that results from the ingestion of toxic substances such as methanol, ethylene glycol, or paraldehyde; and a component of the acidosis of kidney failure. Another rare but underdiagnosed cause of severe, high anion gap metabolic acidosis in adults is that due to accumulation of 5-oxoproline (pyroglutamic acid). Reported are four patients with this syndrome, and reviewed are 18 adult patients who were reported previously in the literature. Twenty-one patients had major exposure to acetaminophen (one only acute exposure). Eighteen (82%) of the 22 patients were women. Most of the patients were malnourished as a result of multiple medical comorbidities, and most had some degree of kidney dysfunction or overt failure. The chronic ingestion of acetaminophen, especially by malnourished women, may generate high anion gap metabolic acidosis. This undoubtedly is an underdiagnosed condition because measurements of serum and/or urinary 5-oxoproline levels are not readily available.

Although systemic hypertension is a common clinical condition, hypertensive emergencies are distinctly unusual in clinical practice. There are some situations, however, that qualify as hypertensive emergencies or urgencies. It is important, therefore, to diagnose these conditions because immediate treatment of severe hypertension is indicated. The diagnosis of hypertensive emergencies depends on the consideration of the clinical manifestations as well as the absolute level of blood pressure. Depending on the target organ that is affected, manifestations of hypertensive emergencies can be quite profound, yet variable. Thus, the physician has to make an accurate clinical diagnosis properly to render appropriate therapy. Fortunately, effective drug therapy is available to decrease blood pressure quickly in hypertensive emergencies. Physicians should be familiar with the pharmacologic and clinical actions of drugs that are used in the treatment of hypertensive emergencies. With proper clinical diagnosis, hypertensive emergencies can be treated successfully and the complications can be prevented with timely intervention. This review discusses the treatment of hypertensive emergencies in general and the therapeutic role of fenoldopam in particular.

Focal segmental glomerulosclerosis (FSGS) is a glomerular disease with a characteristic pathologic presentation that includes segmental scarring involving some but not all glomeruli. On immunofluorescence, deposits of immunoglobulin (Ig) M and C3 may be found in the areas of segmental scarring. Electron microscopy typically demonstrates diffuse epithelial cell foot process effacement and focal areas of retraction of glomerular basement membrane with collapse of the involved tuft (1). Due to the focal nature of the process, it is sometimes challenging to recognize this lesion in the biopsy specimen. Accordingly, special attention needs to be directed at the corticomedullary regions of the kidney where FSGS is more likely to be found. Otherwise, an errant diagnosis of minimal change disease could be made. Once underlying causes of this particular glomerular presentation are ruled out (such as obesity, sleep apnea, heroin abuse, reflux nephropathy, and HIV), one is left with a diagnosis of primary or idiopathic FSGS. It is important to identify patients who present with nephrotic-range proteinuria and have FSGS because early treatment of these patients may alter the course of the disease and prevent relentless progression to terminal renal failure (2). The collapsing form of FSGS, which occurs more commonly in African American patients than in Caucasians, carries a particularly poor prognosis with respect to renal survival (3). This variant is morphologically similar to the glomerular lesion often associated with HIV infection. However, the term idiopathic collapsing glomerulopathy is reserved for patients who are HIV negative. Collapsing glomerulopathy has been associated with non–HIV-related pathologies. These include associations with medications like pamidronate and interferon-alfa and with viral infections like parvovirus B19, cytomegalovirus, and hepatitis C (4, 5). Rarely, multiple myeloma has been associated with this lesion (6, 7). A case of collapsing FSGS in a patient with parvovirus B19 infection is presented with review of the known literature.

African-American patients constitute a significant and important group who are at high risk for developing hypertension-related complications. The proportion of African-American patients succumbing to or suffering from cardiovascular, renal, and neurologic sequelae is unacceptably high. Therefore, it is extremely crucial to develop appropriate therapeutic strategies for this vital subset of our society. The renin-angiotensin system may play a role in the pathophysiology of hypertension-related diseases, and therefore drugs that block this system, ie, angiotensin converting enzyme inhibitors and angiotensin receptor blockers, may have a special indication for African-American patients. Although these drugs may not be the most efficacious agents in terms of blood pressure reduction, they have a major benefit in offering target organ protection and arresting disease progression in the African-Americans. Hence, contrary to the old notions, drugs blocking the renin-angiotension system have an important place in the management of hypertension and related disorders in African-American patients.