This review provides a summary and assessment of research involving renal prostaglandins. Arachidonic acid released from phospholipids is converted by prostaglandin cycle-oxygenase in the kidney to PGE2, PGF2α, PGD2, and, possibly, to PGI2, and thromboxane A2. Production of PGE2, and PGF2α, is predominately but not exclusively in the medulla, whereas degradative enzymes are present in both cortex and medulla. Prostaglandins enter the tubular lumen by facilitated transport and are partially reabsorbed from the urine in the distal nephron. Urine prostaglandins probably reflect renal synthesis. PGE2 and endoperoxides stimulate and PGF2α and indomethacin inhibit renal renin synthesis. In response to ischemia, vasoconstriction, or angiotensin II the kidney increases prostaglandin synthesis to modulate renal vascular resistance. In conscious animals or man no role has been established for prostaglandins in the maintenance of basal renal blood flow or renal sodium excretion. PGE influences renal water excretion by inhibiting the action vasopressin. Despite conflicting data there is evidence that renal prostaglandins are involved either primarily or secondarily in many types of hypertension. Inhibitors of prostaglandin cyclooxygenase have been used with success in Bartter's syndrome. Conflicting results in many areas of investigation may be resolved by the use of more accurate and reliable assays, careful handling of samples, and the use of urine to further investigate renal prostaglandin synthesis. prostaglandin synthesis; renin-angiotensin; hypertension; antidiuretic hormone

Family caregivers play a major role in maximizing the health and quality of life of more than 30 million individuals with acute and chronic illness. Patients depend on family caregivers for assistance with daily activities, managing complex care, navigating the health care system, and communicating with health care professionals. Physical, emotional and financial stress may increase caregiver vulnerability to injury and illness. Geographically distant family caregivers and health professionals in the role of family caregivers may suffer additional burdens. Physician recognition of the value of the caregiver role may contribute to a positive caregiving experience and decrease rates of patient hospitalization and institutionalization. However, physicians may face ethical challenges in partnering with patients and family caregivers while preserving the primacy of the patient-physician relationship. The American College of Physicians in conjunction with ten other professional societies offers ethical guidance to physicians in developing mutually supportive patient-physician-caregiver relationships.

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To investigate whether changes in systemic pH affect intracellular pH (pHi), energy-rich phosphates, and lactic acid generation in muscle, eight normal volunteers performed exhaustive forearm exercise with arterial blood flow occluded for 2 min on three occasions. Subjects ingested 4 mmol/kg NH4Cl (acidosis; A) or NaHCO3 (alkalosis; B) or nothing (control; C) 3 h before the exercise. Muscle pHi and phosphocreatine (PCr) content were measured with 31P-nuclear magnetic resonance (31P-NMR) spectroscopy during exercise and recovery. Lactate output during 0.5-7 min of recovery was calculated as deep venous-arterial concentration differences times forearm blood flow. Before exercise, blood pH and bicarbonate were lower in acidosis (7.303 +/- 0.009, 18.6 +/- 0.5 meq/l) than alkalosis (7.457 +/- 0.010, 32.2 +/- 0.7 meq/l) and intermediate in control (7.389 +/- 0.007, 25.3 +/- 0.6 meq/l). Lactic acid output during recovery was less with A (245 +/- 39 mumol/100 ml) than B (340 +/- 55 mumol/100 ml) (P less than 0.05) and intermediate in C (293 +/- 31 mumol/100 ml). PCr utilization and resynthesis were not affected by extracellular pH changes. pHi did not differ before exercise (A, 7.04 +/- 0.01; B, 7.09 +/- 0.01; C, 7.06 +/- 0.01) or at its end (A, 6.28 +/- 0.07; B, 6.28 +/- 0.11; C, 6.31 +/- 0.09). Hence systemic acidosis inhibited and alkalosis stimulated lactic acid output. These findings suggest that systemic pH regulates cellular acid production, protecting muscle pH, at the expense of energy availability.

Metabolic acidosis is a feature of chronic kidney disease (CKD), but whether serum bicarbonate concentration is influenced by variations in dietary protein intake is unknown. For assessing the effect of diet, data that were collected in the Modification of Diet in Renal Disease study were used. In this study, patients with CKD were enrolled into a baseline period, then randomly assigned to follow either a low-or a usual-protein diet (study A, entry GFR 25 to 55 ml/min) or a low-or very low-protein diet, the latter supplemented with ketoanalogs of amino acids (study B, entry GFR 13 to 24 ml/min). Serum [total CO 2 ] and estimated protein intake (EPI) were assessed at entry (n ‫؍‬ 1676) and again at 1 yr after randomization, controlling for changes in GFR and other key covariates (n ‫؍‬ 723 ]) falls as GFR decreases in chronic kidney disease (CKD) (1,2), but the values vary widely among patients with similar levels of kidney function. Part of this difference may be due to dietinduced differences in endogenous acid production. In individuals with normal kidney function, the effect of diet on serum [total CO 2 ] is small and not detectable unless the influence of Paco 2 is removed (3). Given the impairment in acid excretion that occurs in CKD (4 -6), one might anticipate that differences in diet-induced acid production would have a greater influence on serum [total CO 2 ] than in people with normal kidney function. The major source of endogenous acid production comes from metabolism of dietary protein (7); therefore, protein restriction should result in an increase in serum [total CO 2 ] if this hypothesis is correct. Despite extensive studies on the effects of protein restriction on metabolic parameters and kidney disease progression (8), little attention has been directed to the effect of this intervention on serum [total CO 2 ] in CKD. In one study in humans with severe CKD, serum [HCO 3 Ϫ ] was notably higher when the patients were compliant with a very low-protein diet (0.3 g/kg body weight) supplemented with ketoanalogs of amino acids (9). In two other studies in humans, serum [total CO 2 ] did not increase significantly after a 50% reduction in protein, but both studies contained very few subjects (10,11). The best data supporting an effect of protein restriction on body alkali stores in CKD come from a partial nephrectomy rat model (12). In this model, steady-state serum [HCO 3 Ϫ ] was significantly higher (by 2 mEq/L) in animals that ingested a low-protein diet (6% of total calories/d) as compared with animals that ingested a normal-protein diet (24% of total calories/d).To determine whether systematic changes in dietary protein intake affect serum [total CO 2 ] in a large cohort of patients with CKD, we evaluated the data collected in patients who participated in the Modification of Diet in Renal Disease (MDRD) study, focusing on GFR, protein intake, and serum [total CO 2 ] (13). Our analysis demonstrates that [total CO 2 ] is inversely related to dietary protein intake in this group of patients and that...

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