Renal excretory function

H24. Hinder, F Booke, M Traber, L. D., Matsumoto, N., Nishida, K Rogers, S and Traber, D. L., Nitric oxide synthase inhibition during experimental sepsis improves renal excretory function in the presence of chronically increased atrial natriuretic peptide. Crit. Care Med. 24,131 -136 (1996). 

However, the physiology of ageing includes poorer gastrointestinal absorption, somewhat reduced hepatic drug metabolism, and, commonly, a loss of lean body mass. While all of these have been documented, none is of as great a significance as the loss of renal excretory function which is invariably present in old age. 

Susic D, Kentera D. 1988. Dependence of the hypertensive effect of chronic vanadate administration on renal excretory function in the rat. J Hypertension 6 199-204. 

The metabolic changes observed in uremia result from the decline in renal excretory function, hence the retention of a legion of substances the loss of vital renal hormones (e.g., erythropoietin) and enzymes (e.g., la-hydroxylase) the effect of the uremic environment on organ function, intermediary metabolism, and transport processes dialysis-related problems and exogenous toxins. 

Edetate disodium, a heavy metal antagonist, is indicated in hypercalcemia (500 mg/kg daily by slow IV infusion) and in digitalis-induced cardiac arrhythmias (15 mg/kg/hour by IV infusion). Ethylenediaminetetraacetic acid (EDTA) will lower serum levels of calcium, magnesium, and zinc. It should not be used in anuria, and renal excretory functions (BUN and creatinine) should be monitored carefully. EDTA should be used cautiously in hypokalemia and in patients with limited cardiac reserve. 

Creatine is synthesized in an interorgan metabolic pathway that spans the kidney and liver. In the kidney, arginine and glycine are condensed to form guanidinoacetate, which is exported from the kidney and taken up by hepatocytes in which it is methylated. Creatine phosphate is chemically rmstable and spontaneously cyclizes to give creatinine and phosphate it cannot be reverted back to creatine, so it is a metabolic end product that is excreted in the urine. Because the size of the creatine phosphate pool is relatively constant, the amount of creatinine produced in 24 h is also relatively constant. Thus, the amoruit of creatinine excreted in the urine is used clinically to gauge renal excretory function. 

In two kidney-one clip hypertensive rabbits without significant impairment of renal function, treatment with indomethacin for 10 days is without effect on blood pressure although it reduces plasma renin activity . In contrast, in two kidney-one clip hypertensive rabbits having high plasma renin activity and depressed renal haemodynamics, chronic treatment with indomethacin aggravates both the hypertension and the renal function impairment . In the latter study, plasma renin activity, which initially was reduced by indomethacin, returned on subsequent days to pretreatment levels pari passu with the increase in blood pressure and the deterioration of renal function . Chronic indomethacin treatment also exacerbates the hypertension, and depresses renal excretory function, in rats with two kidney-one clip hypertension . However, short-term treatment with indomethacin lowers blood pressure, associated with reduction of plasma renin activity, in rats with two clip—one kidney hypertension . Indomethacin also produces correlated decrements of blood pressure and plasma renin activity in rats made hypertensive by complete ligation of the aorta between the renal arteries . In contrast, shortterm treatment with indomethacin or meclofenamate is without effect on blood pressure in dogs with two kidney—one clip hypertension . 

Although many factors undoubtedly modify the pathogenesis of hypertension, the bulk of evidence points toward the kidney as the focal point. Future studies directed toward a careful definition of renal prohypertensive and antihypertensive factors coupled with renal excretory function and autonomic nerve activity would appear to be most likely to yield the ultimate solution to this complex problem. 

There are many similarities between human essential hypertension and experimental renal hypertension. To mention a few In both cases cardiac rate and output, blood volume, and blood viscosity, as well as peripheral blood flow, are normal. Renal blood flow seems to be reduced, while renal excretory function remains normal in the benign phase of both the human and the experimental disease and becomes reduced in the malignant phase. In both types of hypertension cardiac hypertrophy occurs and is chiefly left ventricular. 

The circulatory status of patients with essential hypertension resembles fundamentally the hypertension produced in animals. There is also clinical evidence that the kidneys are diseased in many patients with hypertension. Fishberg (45) and Bell and Clawson (10), as well as Moritz and Oldt (115), have found oi anic arteriolar disease in the kidneys of a majority of patients who had essential hypertension with or without signs of disturbed renal excretory function. Furthermore, renal ischemia was found to be present in many hypertensive patients (169). This ischemia seemed to be the result of the presence of vasoconstrictor substances in the blood, since it was readily reversible by agents which produce renal hyperemia in normal persons. Smith, Goldring, and Chasis (169) investigated the impairment of renal blood flow in 21 hypertensive patients. In none of these patients did the authors find unilateral impairment of the renal blood flow. 

Most drugs are cleared by elimination of unchanged drug by the kidney and/or by metabolism in the liver. For a drug eliminated primarily via renal excretory mechanisms, impaired renal function may alter its pharmacokinetics (and pharmacodynamics) to an extent that the dosage regimen needs to be changed from that used in patients with normal renal function. 

This patient has a massively raised ALT, indicating considerable hepato-cyte damage. All functions of the liver are likely to be affected, including reduced secretory and excretory function, demonstrated in this case by a raised bilirubin reduced synthetic function, shown by the raised INR (albumin is imaffected at this time due to its long half life) reduced metabolic function, indicated by accumulation of ammonia and other toxins leading to encephalopathy. Blood flow through the liver is likely to be unaffected, as there is no cirrhosis/portal hypertension. As with all other functions of the liver, this patient s ability to metabolise drugs is likely to be severely affected. Renal function is also impaired secondary to paracetamol toxicity. 

Adults with normal excretory functions should not be at risk, but those with renal failure are hkely to experience complications (SEDA-17, 425) (SEDA-18, 374). 

Metabolic bone diseases result from a partial uncoupling or imbalance between bone resorption and formation. Decreased bone mass, or osteopenia, is more common than abnormal increases of bone mass. The most prevalent metabolic bone diseases are osteoporosis, osteomalacia and rickets, and renal osteodystrophy. Osteoporosis, the most prevalent metabolic bone disease in developed countries, is characterized by loss of bone mass, microarchitectural deterioration of bone tissue, and increased risk of fracture. Rickets and osteomalacia, which are more common in the less-developed countries, are characterized by defective mineralization of bone matrix. Renal osteodystrophy is a complex condition that develops in response to abnormalities of the endocrine and excretory functions of the kidneys. These three metabolic bone diseases and Paget s disease, a localized bone disease, are discussed below followed by laboratory markers of bone metabolism. 

PRITCHARD, J.B. and JAMES, M.O. (1982) Metabolism and urinary excretion. In Metabolic Basis of Detoxication, edited by W.B.Jakoby, J.R.Bend and J.Caldwell (New York Academic Press). PRITCHARD, J.B. and MILLAR, D.S. (1993) Mechanisms mediating renal secretion of organic anions and cations. Physiolog. Rev., 73, 765-796. SMITH, R.L. (1973) The Excretory Function of Bile (London Chapman Hall). 

In rabbits with one kidney-one clip hypertension, treatment with indomethacin for 10 days aggravates the hypertension and causes deterioration of renal haemodynamic and excretory functions, while reducing plasma renin activity . In contrast, short-term treatment with indomethacin was reported to reduce both blood pressure and plasma renin activity in dogs with one kidney-one clip hypertension . Treatment with meclofenamate prior to and following bilateral renal artery constriction markedly attenuates, in the acute phase, the development of hypertension in rats. However, once the... 

The renal kallikrein-kinin [40] system has been suggested as influencing renal hemodynamic as well as excretory function. This activity may also be linked to arachidonate metabolites, like PGEj, since increased excretion of cyclooxygenase products are associated with increased kallikrein-kinin excretion. However, the physiological significance of this relationship is uncertain. 

Despoponlos, A. Kopp, A. Simms, Q. Congruence of renal and hepatic excretory functions. Sulfonic acid dyes. Am. J. Physiol. 1971, 220, 1755-1758. 

The remission of hypertension which was associated with wei t loss in this patient is probably an important factor in the improvement of the renal excretory capacity for urate and an impairment of urate clearance by hypertension is well docvimented (9, 10, 11). In addition, his daily production of urate per mit surface area fell considerably with weight reduction, which implies that urate production in an individual may be greater in absolute terms when he is obese than at normal body size. The study also shows that the daily production of urate in an individual is not a constant function, but is susceptible to a variety of exogenous inferences. 

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