De novo NAD+ biosynthetic impairment in acute kidney injury in humans.

Nicotinamide adenine dinucleotide (NAD+) extends longevity in experimental organisms, raising interest in its impact on human health. De novo NAD+ biosynthesis from tryptophan is evolutionarily conserved yet considered supplanted among higher species by biosynthesis from nicotinamide (NAM). Here we show that a bottleneck enzyme in de novo biosynthesis, quinolinate phosphoribosyltransferase (QPRT), defends renal NAD+ and mediates resistance to acute kidney injury (AKI). Following murine AKI, renal NAD+ fell, quinolinate rose, and QPRT declined. QPRT+/- mice exhibited higher quinolinate, lower NAD+, and higher AKI susceptibility. Metabolomics suggested an elevated urinary quinolinate/tryptophan ratio (uQ/T) as an indicator of reduced QPRT. Elevated uQ/T predicted AKI and other adverse outcomes in critically ill patients. A phase 1 placebo-controlled study of oral NAM demonstrated a dose-related increase in circulating NAD+ metabolites. NAM was well tolerated and was associated with less AKI. Therefore, impaired NAD+ biosynthesis may be a feature of high-risk hospitalizations for which NAD+ augmentation could be beneficial.

Successful return to peritoneal dialysis after a case of relapsing Sphingomonas paucimobilis peritonitis
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Sphingomonas paucimobilis is an uncommon source of peritonitis in patients undergoing peritoneal dialysis (PD). Although only a small number of cases have been reported, treatment failure rate is extremely high, with removal of the peritoneal dialysis catheter noted in ~ 50% of reported cases. The potential damage to the peritoneal membrane from peritonitis with this organism and the ability to return to PD after infection is unknown. We report a unique case in which a patient was able to successfully return to PD after relapsing Sphingomonas paucimobilis peritonitis, without apparent effects to dialysis clearance or ultrafiltration.
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The Will to Live: Preservation of a Forearm Loop Arteriovenous Graft via Development of Median Cubital Venous Collateral Circulation.

BACKGROUND: Forearm loop arteriovenous grafts most commonly fail because of stenosis, with thrombosis at the venous anastomosis. Treatment begins with identification of the stenotic lesion causing thrombosis, followed by either a percutaneous method using thrombolytic agents with possible balloon angioplasty and mechanical evacuation or surgical thrombectomy. CASE REPORT: We present a case of thrombosis in a forearm loop graft with successful percutaneous thrombectomy. Preservation of this access site was only possible because of an unusual finding of collateral circulation, with the median cubital vein acting as a conduit to the basilic vein. CONCLUSION: The choice of surgical vs percutaneous methods for treating a thrombosed graft remains controversial. Yet the success rates of pharmacologic thrombolysis and the percutaneous approach are comparable to those of surgical thrombectomy. Our case of successful percutaneous thrombectomy illustrates the value of preserving the median cubital vein whenever possible in the placement of forearm arteriovenous grafts.

Distended bladder presenting with altered mental status and venous obstruction.

BACKGROUND: New onset or acute worsening of bilateral lower extremity swelling is commonly caused by venous congestion from decompensated heart failure, pulmonary disease, liver dysfunction, or kidney insufficiency. A thromboembolic event, lymphatic obstruction, or even external compression of venous flow can also be the culprit. CASE REPORT: We report the case of an 83-year-old male with a history of myelodysplastic syndrome that progressed to acute myeloid leukemia, bipolar disorder, and benign prostatic hypertrophy. He presented with altered mental status and new onset lower extremity edema caused by acute bladder outflow obstruction. Computed tomography of the abdomen and pelvis showed the patient's distended bladder compressing bilateral external iliac veins. CONCLUSION: Insertion of a Foley catheter resulted in several liters of urine output and marked improvement in his lower extremity edema and mental status a few hours later. Our extensive workup failed to reveal a cause of the patient's acute change in mental status, and we attributed it to a concept known as cystocerebral syndrome.

CLINICAL CASE OF THE MONTH. A 63-Year-Old Woman With Rash and Proximal Muscle Weakness.

A 63-year-old woman with a history of infiltrating ductal breast cancer, status post-mastectomy and chemotherapy, was in remission for 18 months prior to being admitted to the hospital with complaints of a pruritic erythematous macular rash involving her head, chest, and bilateral upper and lower extremities. Along with the dermatologic manifestations, physical exam revealed proximal symmetrical muscle weakness and bilateral axillary lymphadenopathy. Initial workup for muscle weakness revealed a creatine kinase of 2,200 IU/L (normal 20-180 IU/L). After administration of intravenous fluids for renal protection, serum sodium dropped to 121 mEQ/L (normal 135-145 mEQ/L). Computed tomography of the chest showed axillary and supraclavicular lymphadenopathy. Biopsy of a supraclavicular node revealed infiltrating ductal cancer with histologic and morphologic characteristics similar to her previous breast cancer. Following an extensive laboratory workup, we concluded that our patient's myositis and hyponatremia were paraneoplastic syndromes secondary to her recurrent breast cancer.