Faculty Bibliography

BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) leads to kidney failure in half of those affected. Increased levels of adenosine 3;:5;-cyclic monophosphate (cAMP) play a critical role in disease progression in animal models. Water loading, by suppressing arginine vasopressin (AVP)-stimulated cAMP production, is a proposed therapy for ADPKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The effects of acute and sustained water loading on levels of urine osmolality (Uosm) and cAMP in 13 subjects with ADPKD and 10 healthy controls were studied. Uosm and cAMP concentrations were measured before and after water loading. RESULTS: Urine [cAMP] indexed to Uosm significantly decreased with acute water loading in both groups (58% in controls and 35% in ADPKD). Chronic water loading resulted in a nonsignificant 13% decrease in 24-hour urine cAMP excretion in ADPKD participants, despite an increase in 24-hour urine volume by 64% to 3.14 +/- 0.32 L and decrease in mean Uosm by 46%, to below that of plasma (270 +/- 21 mOsm/L). CONCLUSIONS: Increased water intake of 3 L per day decreased Uosm in most ADPKD subjects. While urine [cAMP] accurately reflects changes in Uosm during acute water loading in ADPKD subjects, chronic water loading did not lower 24-hour urine cAMP excretion, although subjects with higher baseline [cAMP] (>2 nmol/mg Cr) responded best. Decreases in urine [cAMP] and osmolality are consistent with decreased AVP activity. These results support the need for a larger study to evaluate the effect of chronic water loading on ADPKD progression

Gout recently passed rheumatoid arthritis to become the most common inflammatory arthritis in the United States (US). However, epidemiologic studies indicate that the quality of gout management is suboptimal owing to both patient and physician issues. Only three options for urate-lowering therapy are currently available in the US: allopurinol, probenecid, and recently, febuxostat. Probenecid is generally safe except for the occurrence of urolithiasis, but is only effective for the subset of patients with better kidney function. Allopurinol use is limited due to its side effects, potential toxicity of uncertain magnitude in patients with renal disease, and failure to achieve targeted serum urate levels. In part this failure may be due to the necessity for it to be titrated for optimal therapeutic effect. Febuxostat is a new medication that may offer several advantages and can be given as an alternative to allopurinol. We review the basic biology and clinical performance of febuxostat, and consider the potential utility of this agent in comparison to the older, better-established gout therapeutics

Extracorporeal removal of drugs and other poisons is occasionally indicated in the management of intoxications. The available modalities include hemodialysis and several methods of continuous renal replacement therapy (CRRT), including continuous venovenous hemofiltration with or without dialysis augmenting drug removal. A growing literature promoting CRRT for extracorporeal removal has been published and is reviewed here. Estimates of clearance achieved by these techniques uniformly demonstrate that hemodialysis achieves higher clearances. CRRT may be appropriate for more hypotensive and unstable patients, though these might be the patients most in need of a more rapidly effective technique. For the most part, these case reports have not demonstrated that CRRT was necessary because of hemodynamic instability. Hemodialysis remains the first choice among modalities of extracorporeal removal with CRRT reserved for patients who truly cannot tolerate hemodialysis

Gout is a chronic disease in which excessively high levels of serum urate (hyperuricemia) result in tissue depositions of sodium urate crystals and intermittent inflammatory attacks. Patients who have gout frequently experience a range of comorbidities, which complicates management and affects long-term prognosis. We review some of the more important of these comorbidities and consider the extent to which gout or hyperuricemia may be either a consequence or a cause of these related conditions. In addition, we briefly consider several neurological conditions in which the presence of gout or a high serum urate level may be associated with less disease, rather than more

Introduction: Extended warm ischemia time during laparoscopic partial nephrectomy can lead to considerable renal injury. Purpose: We examined the ability of a unique renoprotective cocktail to minimize and reverse warm ischemia-reperfusion injury. Materials and Methods: A warm renal ischemia model was developed using Sprague-Dawley rats (N=18). The left renal artery was clamped for 40 minutes, followed by 48 hours of reperfusion. A renoprotective cocktail referred to as GPM (a mixture of specific <Graph presented> growth factors and biochemicals) was given subcutaneously at 24 hours, 0 hours and24 hours after surgery. At 48 hours, both kidneys were harvested and examined with hematoxylin-eosin and periodic acid-Schiff (PAS) stains. Medullary tubular damage was graded 0-5 based on morphological changes (loss of brush border, necrosis and areas of red cell extravasation). Western blot analysis was performed using ischemia marker neutrophil gelatinase associated lipocalin (N-GAL). Non-parametric statistical considerations were performed (a=0.05). Results: Results are illustrated in Figure 1. GPM treated kidneys showed a statistically significant decrease in warm ischemiareperfusion injury as compared to ischemic controls (p<0.01). Additionally, Western blot analysis revealed ischemia marker NGAL was reduced in GPM treated kidneys. Conclusions: By histopathologic and molecular measures our unique renoprotective cocktail minimized and reversed warm ischemia-reperfusion injury

Chronic kidney disease (CKD) is a risk factor for poor outcomes in patients with coronary artery disease (CAD), but it is unknown whether CKD influences the efficacy of alternative CAD treatment strategies. Thus, we compared outcomes in stable CAD patients with and without CKD randomized to percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) or OMT alone in a post hoc analysis of the 2,287 patient COURAGE study. At baseline, 320 patients (14%) had CKD defined as a glomerular filtration rate of <60 mL/min/1.73 m(2), as estimated by the abbreviated 4-variable Modification of Diet in Renal Disease equation. The patients with CKD were older (68 +/- 9 vs 61 +/- 10 years; p <0.001) and more often had diabetes mellitus (42% vs 33%; p = 0.002), hypertension (81% vs 65%; p <0.03), heart failure (13% vs 3.4%; p <001), and three-vessel CAD (37% vs 29%, p = 0.01). After adjustment for these differences, CKD remained an independent predictor of death or nonfatal myocardial infarction (hazard ratio 1.48, 95% confidence interval 1.15 to 1.90). PCI had no effect on these outcomes. Furthermore, at 36 months, a similar percentage of patients with CKD treated with OMT (70%) and PCI plus OMT (76%) were angina free compared to patients without CKD. In conclusion, CKD is an important determinant of clinical outcomes in patients with stable CAD, regardless of the treatment strategy. Although PCI did not reduce the risk of death or myocardial infarction when added to OMT for patients with CKD, it also was not associated with worse outcomes in this high-risk group