Renal ischemia

Sulfinpyrazone, a uricosuric congener of phenylbutazone, also causes hemodynamically-mediated acute renal failure. Sulfinpyrazone inhibition of renal prostaglandin synthesis or reduction of renal kallikrein-kinin activity may imbalance renal hemodynamics, causing renal ischemia. Renal insufficiency may be transient despite continued sulfinpyrazone administration or prolonged and oliguric with a low urinary sodium concentration. 

Kidney Function. Prostanoids influence a variety of kidney functions including renal blood flow, secretion of renin, glomerular filtration rate, and salt and water excretion. They do not have a critical role in modulating normal kidney function but play an important role when the kidney is under stress. Eor example, PGE2 and -I2 are renal vasodilators (70,71) and both are released as a result of various vasoconstrictor stimuli. They thus counterbalance the vasoconstrictor effects of the stimulus and prevent renal ischemia. The renal side effects of NSAIDS are primarily observed when normal kidney function is compromised. 

Evaluation of inhibition of the other isoforms is still in the preclinical stages. Inhibition of NHE2 with prostaglandin E2 or with amiloride hastens the reestablishment of barrier function after intestinal ischemic damage in pigs and the use of S-3226 in rats with renal ischemia improved outcomes. Further work examining the effect of inhibition of the other isoforms is still required. 

There is significant controversy over the role of loop diuretics in the treatment of ARE Theoretical benefits in hastening recovery of renal function include decreased metabolic oxygen requirements of the kidney, increased resistance to ischemia, increased urine flow rates that reduce intraluminal obstruction and filtrate backleak, and renal vasodilation.6 Theoretically, these effects could lead to increased urine output, decreased need for dialysis, improved renal recovery, and ultimately, increased survival. However, there are conflicting... 

Gudmundsdottir H, Haraldsdottir F, Baldursdottir A, et al. Protein expression within the human renal cortex and renal cell carcinoma the implication of cold ischemia. Cell Preserv. Technol. 2007 5 85-92. 

Nonpeptide receptors Adenosine Aj Human cDNA Cardiac arrhythmia, asthma, myocardial ischemia, obesity, pain, renal disease, sleep apnea, stroke, cancer, inflammation, glaucoma, cystic fibrosis, Alzheimer s disease, Parkinson s disease Bradycardia, lipolysis inhibition, reduction of glomerular filtration and natriuresis, tubero-glomerular feedback, antinociception, renal vasodilatation-constriction, reduction of central cholinergic and noradrenergic nerve activity, presynaptic inhibition of excitatory neuro transmission... 

P743 was tested on a validated multiple-insult rat model [35] involving transient renal ischemia, dehydration, uninephrectomy and selective injection of a high dose (about 1.8 gl kg ) into the single remaining kidney and was found to have only minimal effects on GFR (evaluated by the endogenous creatinine clearance) and induced moderate enzymuria (NAG release into the final urine) or proteinuria. The effects observed were lower than those of the HOCA diatri-zoate [25]. 

Parenteral Therapy in the hospitalized patient may be initiated IV or IM. Use parenterally only when the drug cannot be given orally. Usual dose is 20 to 40 mg, repeated as necessary. Certain patients (especially those with marked renal damage) may require a lower dose. Check blood pressure frequently it may begin to fall within a few minutes after injection average maximal decrease occurs in 10 to 80 minutes. Where there is a previously existing increased intracranial pressure, lowering the blood pressure may increase cerebral ischemia. Most patients can transfer to the oral form in 24 to 48 hours. 

Fujii, T., Takaoka, M., Muraoka, T., Kurata, H., Tsuruoka, N., Ono, H., Kiso, Y., Tanaka, T., and Matsumura, Y. (2003). Preventive effect of L-carnosine on ischemia/reperfusion-induced acute renal failure in rats. Eur.. Pharmacol. 474, 261-267. 

Uses Acute migraine Action S otonin 5-HTi rec tor antagonist Dose 1—2.5 mg PO once r eat PRN in 4 h 5 mg/24 h max -1- in mild renal/hepatic insuff, take w/ fluids Caution [C, M] Contra Sev e renal/hepatic impair, avoid w/ angina, ischemic heart Dz, uncontrolled HTN, cerebrovascular synds, CTgot use Disp Tabs SE Dizziness, sedation, GI upset, paresthesias, ECG changes, coronary vasospasm, arrhythmias Interactions T Effects W/ MAOIs, SSRIs T effects OF CTgot drugs X effects W7 nicotine EMS May T PR or CyT int val, monitor ECG OD May cause profound HTN and cardiac ischemia symptomatic and supportive... 

Condeelis J (1993) Life at the leading edge the formation of cell protrusions. Annu Rev Cell Biol 9 411 44 Da T, Verkman AS (2004) Aquaporin-4 gene disruption in mice protects against impaired retinal function and cell death after ischemia. Invest Ophthalmol Vis Sci 45 4477 483 Deen PM, Verdijk MA, Knoers NV, Wieringa B, Monnens LA, van Os CH, van Oost BA (1994) Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science 264 92-95... 

Parke-Davis workers have performed SAR studies on endothelin receptor antagonists derived from a dimethoxy-substituted oxicam in the search of treatments for hypertension, congestive heart failure, renal failure, pulmonary hypertension, ischemia, and cerebral vasospasm <1998BMC1447>. Compound 295 displayed a 40-fold selectivity for endothelin receptor antagonist A (ETa) over endothelin receptor antagonist B (ETb) (Figure 26). 

Kakoki M et al Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury. Proc Natl Acad Sci U S A 2007 104 7576. [PMID 17452647]... 

---