The patient in the case presents a nephrotic syndrome, so far so good. As for the diet, to reduce edema in these patients, it is recommended that it be low-protein and low-salt, so options 1 and 3 would be true. ACE inhibitors are also administered as primary treatment for nephrotic syndrome, since they decrease urinary protein excretion, as do ARA II and loop diuretics, so options 2 and 5 would also be correct. Therefore, simply by discarding, we are left with option 4 as false, and therefore, the correct answer. Moreover, it should stand out from the beginning as the option to be marked, since precisely one of the causes of nephrotic syndrome is the intake of NSAIDs, so how could they be indicated in the treatment?

The patient in the case presents a nephrotic syndrome, so far so good. As for the diet, to reduce edema in these patients, it is recommended that it be low-protein and low-salt, so options 1 and 3 would be [HIDDEN]. ACE inhibitors are also administered as primary treatment for nephrotic syndrome, since they decrease urinary protein excretion, as do ARA II and loop diuretics, so options 2 and 5 would also be [HIDDEN]. Therefore, simply by discarding, we are left with option 4 as [HIDDEN], and therefore, [HIDDEN]. Moreover, it should stand out from the beginning as the option to be marked, since precisely one of the causes of nephrotic syndrome is the intake of NSAIDs, so how could they be indicated in the treatment?

A 42-year-old man came to consultation for edema. Initial tests showed the presence of proteinuria of more than 10 grams/24 hours. Which of the following measures is NOT indicated in the treatment of this patient?

Administration of angiotensin-converting enzyme inhibitors.

[The effect of a low-protein diet and certain pharmaceutical agents on the course of ablation nephropathy in rats].

The beneficial effect of a low-protein diet on the course of renal failure after ablation nephropathy in the rat is known; also calcium channel antagonists (CaA) and angiotensin I converting enzyme inhibitors (ACEI) have a protective effect. Because even simple energy restriction retards the development of spontaneous or ablation-induced glomerulosclerosis the authors decided to replace the lacking dietary protein in the low protein diet by starch (disaccharide) and by fat (cereal oil) and compare these two low-protein diets as to their effect on the development of chronic renal failure (CRI) caused by surgical removal of 5/6 of renal parenchyma (5/6 NX). In Wistar rats just after weaning, 5/6 of renal parenchyma were removed surgically. Thereafter, the rats were fed either a "high-protein" (21%) or two types of a "low-protein" (6%) diet, in one of the latter, the lack of protein was substituted by saccharide, in the other by fat making the substitution "isocaloric" in either case. In all three diet groups, subgroups drinking either tap water or water containing either the ACE-inhibitor enalapril (ena) or the calcium antagonist diltiazem (dil) or both (ena+dil) were formed. On the high-protein diet, an increase in the weight of kidney remnants, in proteinuria and in systolic blood pressure (SBP) was seen. This was prevented by feeding either type of the low-protein diet but also by ena and ena+dil. Ena and ena+dil not only prevented the increase in SBP but actually lowered it significantly. Dil alone also had a SBP-lowering action but offered no protection from kidney hypertrophy and it significantly. Dil alone also had a SBP-lowering action but offered no protection from kidney hypertrophy and proteinuria. No additive protective action of ena+dil or ena+low-protein or ena+dil+low-protein was seen suggesting that the lower limit of these protective actions was reached by the low-protein diet alone. There was no substantial difference between either type of low-protein diet except a small and transient decrease in body weight in the first week on a fat-rich diet. In the described experiments and with the set-up used the low-protein diet had no effect on the plasma creatinine and urea levels nor on creatinine clearance. The weight of the kidney remnants and proteinuria were significantly higher in animals on a high-protein diet who drank water or water with diltiazem. These changes were suppressed by administration of angiotensin converting enzyme inhibitors either alone or combined with diltiazem. A low- protein diet (both types tested) as well as angiotensin converting enzyme inhibitors improve the course of chronic renal failure in ablation nephropathy in the rat; the authors did not prove an additive effect of the combination of this diet with angiotensin converting enzyme inhibitors.

Diuretic effects of angiotensin-converting enzyme inhibition: comparison of low and liberal sodium diet in hypertensive patients.

Inhibitors of the angiotensin-converting enzyme (ACE) acutely increase sodium excretion. Whether or not continued treatment induces net negative sodium balance is not clear, and may depend on initial sodium balance. We therefore investigated the effects of 8 days of treatment with enalapril, 10 mg b.i.d., on sodium balance in 10 subjects with uncomplicated essential hypertension, in balance on a low (50 mmol sodium/24 h) and a liberal (200 mmol sodium/24 h) sodium intake. Sodium excretion exceeded intake during the first days of treatment, amounting to sodium losses of 101 +/- 24 and 112 +/- 15 mmol in the low and the liberal sodium diets, respectively. The sodium loss was accompanied by a fall in body weight with both regimens. The blood pressure response to enalapril was potentiated by the sodium-restricted diet. The net increase in sodium excretion after enalapril administration, however, was similar for both diets. This was particularly true for individual patients, suggesting an individual response pattern to ACE inhibition.

[Management of idiopathic nephrotic syndrome in childhood].

The management of idiopathic nephrotic syndrome (INS) in children includes immunosuppressive and symptomatic treatment. The response to corticosteroid therapy is the best prognostic marker of the disease. The majority of children with INS (about 85%) are steroid-sensitive as they normalize proteinuria within 4 weeks of daily, oral prednisone administration. The most of steroid-sensitive patients (94%) has minimal change of nephrotic syndrome, while the majority (80.5%-94.4%) of those who are steroid-resistant has focal segmental glomerulosclerosis or mesangioproliferative glomerulonephritis. Initial therapy of INS consists of 60 mg/m2/day prednisone daily for 4 weeks followed by 40 mg/m2 on alternate days for 4 weeks, thereafter decreasing alternate day therapy every month by 25% over the next 4 months. Thus, the overall duration of the initial corticosteroids course is 6 months that may be significantly protective against the future development of frequent relapses. Approximately 30% of patients experience only one attack and are cured after the first course of therapy; 10-20% have only 3 or 4 steroid-responsive episodes before permanent cure; the remaining 40-50% of patients are frequent relapsers, or steroid-dependent. Standard relapse therapy consists of 60 mg/m2/ day prednisone until urine is protein free for at least 3 days, followed by 40 mg/m2 on alternate days for 4 weeks. The treatment of frequent-relapses and steroid-dependent INS includes several different regimens: maintenance (6 months) alternate steroid therapy just above steroid threshold (0.1-0.5 mg/kg/48h), levamisole, alkylating agents (cyclophosphamide or chlorambucil) or cyclosporine. The worse prognosis is expected in steroid-resistant patients who are the most difficult to treat. Renal biopsy should be performed in them. At present, there is no consensus on therapeutic regimen for steroid-resistant patients. The following immunosuppressive drugs have been used with varying success: cyclosporine, intravenous methyl prednisone pulses alone or combined with or followed by alkylating agents, plasma-exchange, and angiotensin-converting enzyme (ACE) inhibitors. Symptomatic treatment includes: 1) dietary regimen with normal protein intake and salt restriction, 2) calcium and vitamin D are prescribed with steroids, 3) diuretics should be used in case of severe edema, 4) infusion of albumin in case of severe hypovolemia, 5) treatment of hypertension, 6) anticoagulant therapy, and 7) prophylactic antibiotics in high-risk patients.

Diuretic and enhanced sodium restriction results in improved antiproteinuric response to RAS blocking agents.

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics may exert synergistic antiproteinuric effects. Eighteen patients with a proteinuria >1 g/24 h after 6 mo of treatment with ramipril at 5 mg/d were assigned to receive in random order ramipril at 10 mg/d, valsartan at 160 mg/d, or combined ramipril at 5 mg/d and valsartan at 80 mg/d in addition to their antihypertensive treatment. The treatment periods lasted 4 wk and were separated by a 4-wk washout with ramipril at 5 mg/d. At the end of this crossover sequence, patients received combined ramipril at 5 mg/d, valsartan at 80 mg/d, and an increased furosemide dosage for an additional 4-wk period. The primary end point was the urinary protein/creatinine ratio for two 24-h urine collections at the end of each treatment period. No significant differences were noted between the study end points of the ramipril 10, valsartan 160, and combined ramipril 5 and valsartan 80 treatment groups. However, the urinary protein/creatinine ratio was lower with combined ramipril 5 and valsartan 80-increased furosemide dosage than with valsartan 160 and combined ramipril 5 and valsartan 80, with a similar tendency compared with ramipril 10. Combined ramipril 5 and valsartan 80-increased furosemide dosage decreased systolic home BP and increased serum creatinine but did not significantly increase the number of symptomatic hypotension cases compared with the other three treatments. Thus, in patients with severe proteinuria and hypertension, a cautious increase in diuretic dosage in addition to combined angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decreases proteinuria and BP but may expose the patient to prerenal failure.

Renal effects of captopril, indomethacin and nifedipine in nephrotic patients after an oral protein load.

In this study we investigated whether the increase in proteinuria induced by an oral protein load may be prevented by the angiotensin-converting enzyme inhibitor (ACEI) captopril in patients with nephrotic syndrome, and whether the effects of captopril on renal haemodynamics and/or glomerular selectivity are comparable to those obtained with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin and the calcium-channel blocker (CaCB) nifedipine. Twelve subjects underwent the following treatments: (1) low-protein meal (0.2 g protein/kg body wt), (2) high-protein meal (1.3 g protein/kg body wt), (3) high-protein meal plus oral captopril (50 mg), (4) high-protein meal plus oral nifedipine (10 mg), (5) high-protein meal plus oral indomethacin (50 mg). Urine and blood samples were obtained after meals and tested for total protein, immunoglobulin G and albumin. GFR and renal plasma flow (RPF) were calculated from iothalamate and p-aminohippuric acid clearances respectively. Mean arterial pressure decreased significantly after both captopril (-4%, P = 0.001) and nifedipine (-5%, P = 0.0019). Compared with the low-protein meal, mean values of GFR and RPF increased significantly after the high-protein meal alone (+21%, P = 0.0002; +10%, P = 0.0491 respectively), and after captopril (+18%, P = 0.0025; +24%, P = 0.0034 respectively) or nifedipine administration (+30%, P = 0.0001; +21%, P = 0.0036 respectively), whereas they remained unchanged after the high-protein meal plus indomethacin administration. FF did not change significantly under the five experimental conditions. The increase in urinary protein excretion induced by the meat load (total protein +18%, P = 0.0102; albumin +26%, P = 0.0316; IgG +28%, P = 0.0203) was entirely blocked by both captopril and indomethacin, whereas it was further increased by nifedipine administration. Both captopril and indomethacin, but not nifedipine, are able to prevent the increase in urinary protein excretion rate following a meat meal. The antiproteinuric effect of captopril is comparable to that of indomethacin, but the renal haemodynamic changes induced by these drugs differ considerably, because the filtration capacity and the renal functional reserve were preserved by captopril and decreased by indomethacin. The reduction in systemic blood pressure following administration of both captopril and nifedipine does not account for changes in proteinuria, since, with a similar degree of blood pressure lowering, urinary protein excretion is reduced by captopril and increased by nifedipine.

Pediatrics_Nelson

NS edema is treated by restricting salt intake. Severe edema may require the use of loop diuretics. When these therapies do not alleviate severe edema, cautious parenteral administration of 25% albumin (0.5 to 1.0 g/kg intravenously over 1 to 2 hours) with an intravenous loop diuretic usually results in diuresis. The administered albumin is excreted rapidly, and, thus, salt restriction and diuretics must be continued. Significant pleural effusions may require drainage. Acute HTN is treated with β-blockers or calcium channel blockers. Persistent HTN usually responds to angiotensin-converting enzyme inhibitors.

Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial.

To compare the effects on proteinuria and blood pressure of addition of dietary sodium restriction or angiotensin receptor blockade at maximum dose, or their combination, in patients with non-diabetic nephropathy receiving background treatment with angiotensin converting enzyme (ACE) inhibition at maximum dose. Multicentre crossover randomised controlled trial. Outpatient clinics in the Netherlands. 52 patients with non-diabetic nephropathy. All patients were treated during four 6 week periods, in random order, with angiotensin receptor blockade (valsartan 320 mg/day) or placebo, each combined with, consecutively, a low sodium diet (target 50 mmol Na(+)/day) and a regular sodium diet (target 200 mmol Na(+)/day), with a background of ACE inhibition (lisinopril 40 mg/day) during the entire study. The drug interventions were double blind; the dietary interventions were open label. The primary outcome measure was proteinuria; the secondary outcome measure was blood pressure. Mean urinary sodium excretion, a measure of dietary sodium intake, was 106 (SE 5) mmol Na(+)/day during a low sodium diet and 184 (6) mmol Na(+)/day during a regular sodium diet (P<0.001). Geometric mean residual proteinuria was 1.68 (95% confidence interval 1.31 to 2.14) g/day during ACE inhibition plus a regular sodium diet. Addition of angiotensin receptor blockade to ACE inhibition reduced proteinuria to 1.44 (1.07 to 1.93) g/day (P=0.003), addition of a low sodium diet reduced it to 0.85 (0.66 to 1.10) g/day (P<0.001), and addition of angiotensin receptor blockade plus a low sodium diet reduced it to 0.67 (0.50 to 0.91) g/day (P<0.001). The reduction of proteinuria by the addition of a low sodium diet to ACE inhibition (51%, 95% confidence interval 43% to 58%) was significantly larger (P<0.001) than the reduction of proteinuria by the addition of angiotensin receptor blockade to ACE inhibition (21%, (8% to 32%) and was comparable (P=0.009, not significant after Bonferroni correction) to the reduction of proteinuria by the addition of both angiotensin receptor blockade and a low sodium diet to ACE inhibition (62%, 53% to 70%). Mean systolic blood pressure was 134 (3) mm Hg during ACE inhibition plus a regular sodium diet. Mean systolic blood pressure was not significantly altered by the addition of angiotensin receptor blockade (131 (3) mm Hg; P=0.12) but was reduced by the addition of a low sodium diet (123 (2) mm Hg; P<0.001) and angiotensin receptor blockade plus a low sodium diet (121 (3) mm Hg; P<0.001) to ACE inhibition. The reduction of systolic blood pressure by the addition of a low sodium diet (7% (SE 1%)) was significantly larger (P=0.003) than the reduction of systolic blood pressure by the addition of angiotensin receptor blockade (2% (1)) and was similar (P=0.14) to the reduction of systolic blood pressure by the addition of both angiotensin receptor blockade and low sodium diet (9% (1)), to ACE inhibition. Dietary sodium restriction to a level recommended in guidelines was more effective than dual blockade for reduction of proteinuria and blood pressure in non-diabetic nephropathy. The findings support the combined endeavours of patients and health professionals to reduce sodium intake. Trial registration Netherlands Trial Register NTR675.

Chronic kidney disease

Screening at-risk people is recommended. Initial treatments may include medications to lower blood pressure, blood sugar, and cholesterol. Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are generally first-line agents for blood pressure control, as they slow progression of the kidney disease and the risk of heart disease. Loop diuretics may be used to control edema and, if needed, to further lower blood pressure. NSAIDs should be avoided. Other recommended measures include staying active, and certain dietary changes such as a low-salt diet and the right amount of protein. Treatments for anemia and bone disease may also be required. Severe disease requires hemodialysis, peritoneal dialysis, or a kidney transplant for survival.

[Comparison of the effects of a low protein diet and angiotensin converting enzyme inhibitors on renal insufficiency in hypertensive rats].

It is known that hypertension to aggravate the course of chronic renal insufficiency (CRI). It is too know the beneficial effect of the angiotensin-converting enzyme inhibitors (ACEI) and the low-protein diet. In this study, the effect of a low protein diet on the course of CRI was compared with that of administration of enalapril (ENA), an ACEI. A new model of genetic hypertension, the Prague Hypertensive Rat (PHR) was used. In rats just after weaning, 5/6 of renal parenchyma were removed surgically (5/6NX). The rats were observed for 8 weeks after 5/6NX. The animals were fed either a normal rat chow containing 23% of protein, or a low-protein diet containing only 6% protein. Control groups drank tap water, experimental groups received water containing ENA at a dose of 5 mg/kg BW. The rats on normal diet drinking water had the highest levels of blood pressure (200 +/- 4.3 mm Hg), proteinuria (56.2 +/- 14.6 mg/24 hours) and heaviest kidney remnants i.e. highest compensatory hypertrophy (2352 +/- 239.4 mg). Both ENA and low-protein diet significantly improved these functions to the same extent. However, a combination of low-protein diet with ENA had no further beneficial effect as against any of these manoeuvres alone. We assume every manoeuvre (low-protein diet and enalapril) exerts a maximal beneficial effect per se: the mechanism of this effect is highly speculative: inhibition of growth factors seems to be the most logical explanation. ACEIs are known to inhibit the production of angiotensin II, low-protein diet should inhibit transforming growth factor beta.

Diffuse proliferative nephritis

If the DPGN is caused by IgA nephropathy then corticosteroids, angiotensin-converting enzyme inhibitor (ACEIs), angiotensin receptor blockers (ARBs), or both ACEIs and ARBs should be used. Corticosteroids are used to suppress the immune system and to reduce inflammation. ACEIs will decrease hypertension by preventing the body from creating angiotensin II, which narrows the blood vessels. ARBs block angiotensin II from acting. The patient's diet should also be changed. The patient should restrict salt intake to improve the hypertension and nephrosis. Protein restriction may reduce the progression of the disease. Fluid restriction may also be necessary if the patient is experiencing edema. Prognosis Prognosis is determined by the stage of the disease. Aggressive therapy is recommended to avoid progressing to end-stage renal disease (ESRD), which is a strong possibility. About 10% of DPGN patients will go into ESRD.

The effect of angiotensin-converting enzyme inhibition and dietary protein restriction in the treatment of proteinuria.

Both angiotensin-converting enzyme inhibitors and dietary protein restriction have been reported to reduce urinary protein losses in patients with chronic glomerular diseases. We evaluated these two therapies in 12 such patients ingesting a constant metabolic diet containing 1.6 g protein/kg body weight per day. After a steady-state was achieved during a 3-week baseline period, patients were randomly assigned to either enalapril, titrated to reduce mean arterial pressure by 10 mm Hg, or an isocaloric 0.8 g/kg protein diet. Five patients in each group completed 3 additional weeks of observation during the treatment period. Enalapril resulted in an average reduction in urinary protein and albumin losses of 26% and 33%, respectively, without reducing creatinine clearance. Albumin synthesis was unchanged and nitrogen balance increased slightly (+142.8 +/- 85.7 mmol/d [+2.0 +/- 1.2 g/d], P = 0.075). Dietary protein restriction had no consistent effect on proteinuria or albuminuria, whereas albumin synthesis (25.9 +/- 3.4 v 21.5 +/- 2.9 g/d/1.73 m2, P less than 0.05) and nitrogen balance (-135.6 +/- 92.8 mmol/d [-1.9 +/- 1.3 g/d], P = 0.10) decreased. Both therapies resulted in a modest increase in plasma potassium concentration. Whether the maintenance of albumin synthesis in the presence of a reduction in urinary protein losses will convey a long-term advantage to treatment of proteinuric patients with angiotensin-converting enzyme inhibitors remains to be determined.

Renal safety of combined cyclooxygenase 2 (COX-2) inhibitor and angiotensin II receptor blocker administration in mild volume depletion.

Drugs that either inhibit prostaglandin synthesis or antagonise angiotensin II effects are likely to impair renal function, especially in patients with an activated renin-angiotensin-aldosterone system. Of the former, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used, and newer agents with cyclooxygenase 2 (COX-2) specific inhibition may have fewer renal side effects compared to non-selective NSAIDs. We therefore investigated whether combination of a COX-2 inhibitor with an angiotensin II subtype 1 (AT1) receptor blocker is safe with regard to preservation of normal renal function in a state of slight volume contraction. Mild volume depletion was induced by a salt-restricted diet in 5 healthy volunteers who were then given a single dose of 400 mg celecoxib, a COX-2 inhibitor, alone or in combination with 150 mg irbesartan, an AT1 receptor blocker. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by measuring inulin and PAH clearance respectively, along with plasma renin activity (PRA) and urinary electrolyte excretion before and over 100 minutes after drug administration. PRA was high prior to drug administration, indicating slight salt depletion, and dropped by 65% after intake of celecoxib alone (p = 0.008) but only by 25% after combined intake with irbesartan (p = n.s.). GFR was not affected either by celecoxib alone or by combined administration with irbesartan. In contrast, ERPF increased by 28% 80 minutes after simultaneous drug intake (p = 0.029), but not after celecoxib alone. Renal sodium and potassium excretion did not significantly change under celecoxib alone or in combination with irbesartan. Selective COX-2 inhibition by celecoxib in combination with an AT1 receptor blocker (irbesartan) has no acute adverse effects on renal haemodynamics and renal salt handling in slightly volume-depleted subjects with normal renal function. Moreover, our data obtained in humans appear to confirm the co-regulatory interaction of COX-2 and angiotensin II in the control of renin release, as suggested by animal studies.

Efficacy and variability of the antiproteinuric effect of ACE inhibition by lisinopril.

We studied the efficacy of the ACE inhibitor lisinopril in treating overt proteinuria in comparison with the NSAID indomethacin, and evaluated some of the conditions that could influence this antiproteinuric effect. In 12 patients with a proteinuria varying from 3.2 to 10.5 g/24 hr, a diastolic BP ranging from 64 to 105 mm Hg, and a GFR varying from 34 to 127 ml/min, the effect of different lisinopril doses and of changing dietary sodium intake was evaluated. Proteinuria fell by 27 +/- 20% from 6.1 +/- 2.1 to 4.5 +/- 1.9 g/24 hr on a low dose (median 5 mg/day) lisinopril and by 50 +/- 17% to 3.1 +/- 1.4 g/24 hr on a higher dose (median 10 mg/day), irrespective of initial proteinuria, BP, or GFR. This antiproteinuric effect was abolished by increasing salt intake from 50 to 200 mmol/day, and was recovered again by re-instituting the sodium restricted diet. The antiproteinuric effect of 10 mg/day lisinopril was comparable to the reduction in proteinuria (by 57 +/- 21% to 2.8 +/- 2.0 g/24 hr) on 150 mg/day indomethacin, while adverse effects were less and renal hemodynamic effects were more favorable during lisinopril. In some patients it took several weeks before the effect of the ACE inhibitor on proteinuria was stabilized. Thus, the antiproteinuric effect of the ACE inhibitor lisinopril appears to be dose and time related, and is strongly dependent on dietary sodium restriction, whereas it does not depend on initial proteinuria, BP, or GFR. The effect is comparable to that of indomethacin, while adverse effects are less.

Fatal hyperkalemia related to combined therapy with a COX-2 inhibitor, ACE inhibitor and potassium rich diet.

We describe the case of a 77-year old mildly hypertensive woman with no underlying renal disease who was admitted to the Emergency Department (ED) in a comatose state with fever. The patient had been on low dose enalapril and a potassium rich diet. Five days before admission, rofecoxib, a new selective COX-2 inhibitor nonsteroidal anti-inflammatory drug (NSAID), was added for leg pain. She was found to have severe hyperkalemia and died 90 min after her arrival. We cannot absolutely determine whether the COX-2 inhibitor was the dominant contributor to the development of hyperkalemia or the combination itself, with an intercurrent infection and some degree of dehydration. Physicians should be aware of this possible complication and only prescribe NSAIDs, including the new COX-2 drugs, to the elderly under close monitoring of kidney function and electrolyte tests.

First-dose phenomenon

The cause is not clear. It occurs more commonly in patients who are salt and fluid volume depleted (as happens due to the use of diuretics), or were using beta blockers. Diuretics and beta blockers are frequently used to control hypertension. For this reason, treatment with prazosin (Minipress) should always be initiated with a low dose and should be taken at bedtime to avoid standing position. Other drug classes with observed first dose hypotension This effect is also observed after the administration of the first dose of drugs in the ACEi class (angiotensin-converting enzyme inhibitor). This may occur with the class's better known side effect of dry cough (due to decreased breakdown of bradykinin), though there is no clear relationship between the two side effects. The first dose phenomenon in ACEi is reduced and made safer by avoiding diuretics for 24 hours prior to first dose, taking first dose at night (so avoiding falls, etc) and starting on low doses and titrating upwards.

The effect of salt restriction and furosemide in patients investigated for renovascular hypertension.

The effect of five days' regimen with a low-sodium diet (approximately 20 mmol Na+ per day) and with 40 mg of furosemide (Lasix) daily on the blood pressure, the renin-aldosterone system and the electrolyte balance was studied in 42 hypertensive patients who received no antihypertensive drugs for four weeks prior to the investigation. Twenty-three of the patients had renal artery stenosis. Both patients with and those without such stenosis showed a significant decrease in systolic and diastolic blood pressure and in the serum concentrations of sodium and potassium and urinary excretion of sodium. A concomitant increase in plasma renin activity in peripheral veins and in urinary excretion of aldosterone was found both in patients without and in those with renal artery stenosis, but in the latter group this response seemed to be less pronounced.

Early administration of angiotensin-converting enzyme inhibitor captopril, prevents the development of hypertension programmed by intrauterine exposure to a maternal low-protein diet in the rat.

1. Associations of intrauterine exposure to maternal undernutrition with later hypertension and coronary heart disease in the human population have been duplicated in the rat. Fetal exposure to low protein diets produces offspring that develop raised systolic blood pressure by the age of weaning. This animal model of 'programmed' hypertension was used to investigate the role of the renin-angiotensin system in the initiation and maintenance of high blood pressure. 2. Pregnant rats were fed diets containing 18 or 9% casein from conception until littering. The offspring from these pregnancies were administered captopril either between 2 and 4 weeks of age, or from 10 to 12 weeks of age. 3. The feeding of low protein diets in pregnancy had no effect upon the reproductive ability of female rats and the offspring generated were of normal birthweight. By 4 weeks of age the male and female offspring of low-protein-fed dams had systolic blood pressures that were 24-25 mmHg higher than those of rats exposed to a control diet in utero. 4. Treatment of 10-week-old female offspring with captopril for 2 weeks indicated that angiotensin II formation may play a role in the maintenance of high blood pressure in low-protein-exposed rats. While captopril had no significant effect upon systolic pressures of rats exposed to the control diet in intrauterine life, the systolic blood pressures of low-protein animals rapidly declined by 31 mmHg. 5. Administration of captopril to male and female offspring between 2 and 4 weeks of age exerted long-term effects upon systolic blood pressure. Eight weeks after cessation of treatment, at an age where maximal blood pressures are achieved, captopril-treated, low-protein-exposed rats had similar blood pressures to normotensive rats exposed to the protein-replete diet in utero. 6. In conclusion, we have demonstrated that the elevation of adult blood pressure associated with fetal exposure to a maternal low-protein diet, is prevented by early administration of an angiotensin-converting enzyme inhibitor. The actions of angiotensin II in the late suckling period may be a critical determinant of long-term cardiovascular functions in these animals.

Additive antiproteinuric effect of converting enzyme inhibition and a low protein intake.

The hypothesis that converting enzyme inhibition and a protein-restricted diet could have additive antiproteinuric effects has been tested. A group of 17 patients with proteinuria in excess of 3 g/24 h per 1.73 m2 of body surface area were submitted to a 3-wk period of study, after a 4-wk wash-out period during which protein intake was 1.0 g/kg per day and in the absence of any medication. During the first and second weeks of the study, protein intake was lowered to 0.3 g/kg per day, and in the third week, it returned to 1.0 g/kg per day. Enalapril (20 mg daily) was administered during the second and third weeks of the study. Initially and at the end of each week thereafter, we determined blood pressure, GFR (inulin clearance), RPF (para-aminohippurate clearance), plasma sodium and potassium, PRA and aldosterone, and the 24-h urine excretion of sodium potassium, protein, and urea. The low protein intake during the first week induced a significant fall of proteinuria (P < 0.01), GFR (P < 0.01), and RPF (P < 0.01) in the absence of changes in filtration fraction. The addition of enalapril induced a further decrease of proteinuria (P < 0.01) and a fall in filtration fraction (P < 0.05), whereas plasma potassium, PRA, GFR, and RPF values increased (P < 0.01). The rise in protein intake during the last week of the study induced a significant rise in proteinuria, GFR, and RPF (P < 0.01), although the first of these parameters attained values significantly lower (P < 0.05) than those observed initially.(ABSTRACT TRUNCATED AT 250 WORDS)

Fibromuscular dysplasia

Children Pediatric FMD medical and surgical treatments or interventions are available. Treatment is determined by factors such as age and disease location but routinely involve controlling hypertension, re-establishing vascular flow, clot prevention, and improving lifestyle such as diet, exercise and smoking cessation. Medical therapy for pediatric population may involve the use of angiotensin-converting enzyme inhibitor (ACE inhibitors) and/or angiotensin II receptor blockers, multiple anti-hypertensive medications, diuretics, calcium channel blockers, and beta-blockers. Prevention of thrombosis of affected arteries may be taken through administration of an antiplatelet medication such as aspirin.

Is "idiopathic" edema idiopathic?

Ten women with "idiopathic" edema had sodium and water retention and a rapid gain in weight when their accustomed intake of diuretics was suddenly stopped. The magnitude of these changes was directly related to the levels of plasma-rening activity before withdrawal of diuretics. Nine patients became edematous. Within 10 days of stopping diuretics, plasma-renin activity and urinary aldosterone excretion decreased to normal or below and within 20 days weight-gain and edema had subsided in seven patients. But the greatest gains in weight, in three patients, were sustained beyond 20 days. Nevertheless, a year later, two of these three patients were free of edema without the use of diuretics. Intermittent edema of unknown cause in most, if not all, otherwise healthy women seems to result from their use of diuretics, abetted in some patients by self-imposed flucuation of sodium and carbohydrate intake, and does not appear to be idiopathic.

Diabetic nephropathy

The status of diabetic nephropathy may be monitored by measuring two values: the amount of protein in the urine - proteinuria; and a blood test called the serum creatinine. The amount of the proteinuria reflects the degree of damage to any still-functioning glomeruli. The value of the serum creatinine can be used to calculate the estimated glomerular filtration rate (eGFR), which reflects the percentage of glomeruli which are no longer filtering the blood. Treatment with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, which dilates the arteriole exiting the glomerulus, thus reducing the blood pressure within the glomerular capillaries, which may slow (but not stop) progression of the disease. Three classes of diabetes medications – GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors– are also thought to slow the progression of diabetic nephropathy.

Captopril challenge test

The captopril challenge test (CCT) is a non-invasive medical test that measures the change in renin plasma-levels in response to administration of captopril, an angiotensin converting enzyme inhibitor. It is used to assist in the diagnosis of renal artery stenosis. It is not generally considered a useful test for children, and more suitable options are available for adult cases. Procedure Plasma concentration of renin is measured prior to and following the administration of captopril. The CCT is considered positive if the renin levels increase substantially or the baseline renin level is abnormally high. An abnormal captopril test is indicative of the presence of renovascular disease. In adults CCT in adults is known to have high sensitivity, but a low specificity. Subtraction angiography is considered a more suitable test for renal artery stenosis in adults. See also captopril suppression test used to diagnose primary aldosteronism References

The blunting of the antiproteinuric efficacy of ACE inhibition by high sodium intake can be restored by hydrochlorothiazide.

Dietary sodium restriction enhances the antiproteinuric and blood pressure lowering effect of ACE inhibition. In clinical practice, however, long-term compliance to a low-sodium diet may be difficult to obtain. We therefore investigated whether the blunting of the antiproteinuric and blood pressure lowering efficacy of ACE inhibition by high sodium intake can be restored by the addition of a diuretic. Seven proteinuric patients with non-diabetic renal disease on chronic ACE inhibition were studied during three consecutive 4-week periods: low sodium (50 mmol/day), high sodium (200 mmol/day) and high sodium plus hydrochlorothiazide (50 mg o.i.d.). During low sodium intake proteinuria was 3.1 (0.7-5.2) g/day, during high sodium intake proteinuria increased to 4.5 (1.6-9.2) g/day (P < 0.05). Interestingly, addition of hydrochlorothiazide again reduced proteinuria to 2.8 (0.6-5.8) g/day (P < 0.05). Mean arterial blood pressure was 89 (84-96), 98 (91-104) and 89 (83-94) mmHg (P < 0.05) during the three periods, respectively. Addition of hydrochlorothiazide can overcome the blunting of the therapeutic efficacy of ACE inhibition on proteinuria and blood pressure by a high sodium intake.

Protein toxicity

Treatment Treatment options for protein toxicity can include renal replacement therapies like hemodialysis and hemofiltration. Lifestyle modifications like a diet low in protein, decreased sodium intake, and exercise can also be in incorporated as part of a treatment plan. Medications may also be prescribed depending on symptoms. Common medications prescribed for kidney diseases include hypertension medications like angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) as they have been found to be kidney protective. Diuretics may also be prescribed to facilitate with waste excretion as well as any fluid retention. A kidney transplant surgery is another treatment option where a healthy kidney is donated from a living or deceased donor to the recipient.

Normal-sodium diet compared with low-sodium diet in compensated congestive heart failure: is sodium an old enemy or a new friend?

The aim of the present study was to evaluate the effects of a normal-sodium (120 mmol sodium) diet compared with a low-sodium diet (80 mmol sodium) on readmissions for CHF (congestive heart failure) during 180 days of follow-up in compensated patients with CHF. A total of 232 compensated CHF patients (88 female and 144 male; New York Heart Association class II-IV; 55-83 years of age, ejection fraction <35% and serum creatinine <2 mg/dl) were randomized into two groups: group 1 contained 118 patients (45 females and 73 males) receiving a normal-sodium diet plus oral furosemide [250-500 mg, b.i.d. (twice a day)]; and group 2 contained 114 patients (43 females and 71 males) receiving a low-sodium diet plus oral furosemide (250-500 mg, b.i.d.). The treatment was given at 30 days after discharge and for 180 days, in association with a fluid intake of 1000 ml per day. Signs of CHF, body weight, blood pressure, heart rate, laboratory parameters, ECG, echocardiogram, levels of BNP (brain natriuretic peptide) and aldosterone levels, and PRA (plasma renin activity) were examined at baseline (30 days after discharge) and after 180 days. The normal-sodium group had a significant reduction (P<0.05) in readmissions. BNP values were lower in the normal-sodium group compared with the low sodium group (685+/-255 compared with 425+/-125 pg/ml respectively; P<0.0001). Significant (P<0.0001) increases in aldosterone and PRA were observed in the low-sodium group during follow-up, whereas the normal-sodium group had a small significant reduction (P=0.039) in aldosterone levels and no significant difference in PRA. After 180 days of follow-up, aldosterone levels and PRA were significantly (P<0.0001) higher in the low-sodium group. The normal-sodium group had a lower incidence of rehospitalization during follow-up and a significant decrease in plasma BNP and aldosterone levels, and PRA. The results of the present study show that a normal-sodium diet improves outcome, and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated CHF patients. Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet.

Acute administration of captopril lowers the natriuretic and diuretic response to a loop diuretic in patients with chronic cardiac failure.

Angiotensin-converting enzyme inhibitors suppress plasma concentrations of the sodium retaining hormones angiotensin II and aldosterone. This action should potentiate the natriuretic and diuretic effects of loop diuretics. Some studies indicate, however, that the introduction of angiotensin-converting enzyme inhibitors for the treatment of cardiac failure is associated with transient weight gain and the development of oedema. We have compared the natriuretic and diuretic response to intravenous frusemide 40 mg alone with the natriuretic and diuretic response to intravenous frusemide 40 mg following the administration of a single dose of captopril in 12 supine male patients with stable chronic cardiac failure. Captopril lowered the 4 h diuretic response to frusemide from 1160 (60) to 685 (77) ml (P less than 0.05) and the natriuretic response from 120 (9.6) to 68 (11.7) mmol (P less than 0.05). Creatinine clearance fell after captopril from 91 (7.2) to 57 (7.7) ml min-1 (P less than 0.05). Systolic and diastolic blood pressures were lower after the administration of captopril but these changes were not significant. Plasma renin activity rose from 3.8 (1.04) to 12.34 (2.94) ng ml h-1 (P less than 0.05) and plasma angiotensin II was reduced from 24.9 (5.05) to 8.14 (1.8) pg ml-1 (P less than 0.05). Plasma aldosterone concentrations were not significantly lower following captopril. Angiotensin-converting enzyme inhibitors cause an acute fall in creatinine clearance which may reduce the effects of loop diuretics and attention must be paid to diuretic dosage when initiating angiotensin-converting enzyme inhibitors for the treatment of cardiac failure.

Sulindac and ibuprofen inhibit furosemide-stimulated renin release but not natriuresis in men on a normal sodium diet.

We compared the effect of two commonly prescribed nonsteroidal anti-inflammatory drugs, ibuprofen and sulindac, and placebo on intravenous furosemide-induced natriuresis and renin stimulation in 11 healthy male volunteers, consuming a 100 mEq sodium, 80 mEq potassium diet. Chronic (6-day) therapy with each agent was followed by a 1-week washout period. There were no significant treatment-related differences in either urine volume or sodium excretion for any of the designated collection periods or for the cumulative value for the 4 h after furosemide administration. Similarly, differences among groups were not observed for creatinine clearance, urinary potassium and urinary chloride excretion. Mean basal plasma renin activity levels prior to furosemide administration on day 6 were significantly lower in the presence of ibuprofen (1.5 +/- 2.0 ng/ml/h;p less than 0.01) and sulindac (2,3 +/- 0.9 ng/ml/h; p less than 0.05), compared with placebo (3.3 +/- 1.1 ng/ml/h); the difference between the two NSAIDs was also significant (p less than 0.05). Mean plasma renin activity levels in the 4 h after furosemide increased significantly at all time points in comparison to basal values, but were significantly less for ibuprofen and sulindac groups in the first hour. Our data suggest that the natriuresis following intravenous furosemide in men consuming a normal sodium intake is not prostaglandin-dependent. Furthermore, the observation that sulindac suppressed basal and stimulated plasma renin activity levels, albeit to a lesser extent than ibuprofen, questions the claim that sulindac "spares' the kidney and compels further evaluation of this issue.

InternalMed_Harrison

Dietary salt restriction and the use of loop diuretics, occasionally in combination with metolazone, may be needed to maintain euvolemia. In contrast, overzealous salt restriction or diuretic use can lead to ECFV depletion and precipitate a further decline in GFR. The rare patient with salt-losing nephropathy may require a sodium-rich diet or salt supplementation. Water restriction is indicated only if there is a problem with hyponatremia. Intractable ECFV expansion, despite dietary salt restriction and diuretic therapy, may be an indication to start renal replacement therapy. Hyperkalemia often responds to dietary restriction of potassium, the use of kaliuretic diuretics, and avoidance of both potassium supplements (including occult sources, such as dietary salt substitutes) and potassium-retaining medications (especially angiotensin-converting enzyme [ACE] inhibitors or angiotensin receptor blockers [ARBs]). Kaliuretic diuretics promote urinary potassium excretion, whereas

IgA nephropathy

The events that tend to progressive kidney failure are not unique to IgA nephropathy and non-specific measures to reduce the same would be equally useful. These include a low-protein diet and optimal control of blood pressure. The choice of the antihypertensive agent is open as long as the blood pressure is controlled to desired level. However, Angiotensin converting enzyme inhibitors and Angiotensin II receptor antagonists are favoured due to their anti-proteinuric effect. In December 2021, budesonide (Tarpeyo) was approved for medical use in the US to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid disease progression.

Enhanced renin levels after discontinuation of furosemide: additional effects of loop diuretics on renin release.

The rate of recovery of the renin-angiotensin-aldosterone axis after stopping diuretic administration was examined in 18 male patients with essential hypertension. Upright plasma renin activity (PRA) and plasma aldosterone (PA) were measured during sodium restriction (10 mEq sodium intake), after three days of furosemide administration (40 mg BID po) and for five days following cessation of the diuretic. After diuretic administration, the mean PRA level (8.2 +/- 1.7 ng/ml/hr) was significantly elevated compared to the level on low sodium diet (4.2 +/- 0.5 ng/ml/hr). However, the major finding was that PRA levels continued to increase significantly compared to levels during diuresis on days 1 (11.3 +/- 1.7 ng/ml/hr) and 2 (10.8 +/- 1.5 ng/ml/hr) of the postdiuretic period. Mean PA values paralleled PRA responses in the study. Infusion of normal saline on postdiuretic day 1 failed to suppress PRA to levels seen in subjects not receiving diuretics. The postdiuretic period was accompanied by increased urinary sodium reabsorption and decreased urinary potassium excretion and by significant decreases in creatinine, PAH and free water clearance. The mechanism of this sustained renin response several days after cessation of diuretic therapy may be best explained by a prolonged action of furosemide or by partial ongoing volume depletion with reduced sodium load to the distal nephron. Since all patients demonstrated a marked and consistent PRA response after diuretic withdrawal, this time period represents a potent stimulatory challenge for monitering renin responses.

Antihypertensive drug

The ratio of CCBs' anti-proteinuria effect, non-dihydropyridine to dihydropyridine was 30 to -2. ACE inhibitors ACE inhibitors inhibit the activity of angiotensin-converting enzyme (ACE), an enzyme responsible for the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor. captopril enalapril fosinopril lisinopril moexipril perindopril quinapril ramipril trandolapril benazepril A systematic review of 63 trials with over 35,000 participants indicated ACE inhibitors significantly reduced doubling of serum creatinine levels compared to other drugs (ARBs, α blockers, β blockers, etc.), and the authors suggested this as a first line of defense. The AASK trial showed that ACE inhibitors are more effective at slowing down the decline of kidney function compared to calcium channel blockers and beta blockers. As such, ACE inhibitors should be the drug treatment of choice for patients with chronic kidney disease regardless of race or diabetic status.

Responsiveness vs. basal activity of plasma ANG II as a determinant of arterial pressure salt sensitivity.

Infusion of angiotensin II (ANG II) causes salt-sensitive hypertension. It is unclear whether this is due to the body's inability to suppress ANG II during increased salt intake or, rather, an elevated basal level of plasma ANG II itself. To distinguish between these mechanisms, Sprague-Dawley rats were instrumented with arterial and venous catheters for measurement of arterial pressure and infusion of drugs, respectively. The sensitivity of arterial pressure to salt was measured in four groups with the following treatments: 1) saline control (Con, n = 12); 2) administration of the angiotensin-converting enzyme inhibitor enalapril to block endogenous ANG II (ANG-Lo, n = 10); 3) administration of enalapril and 5 ng.kg(-1).min(-1) ANG II to clamp plasma ANG II at normal levels (ANG-Norm, n = 10); and 4) administration of enalapril and 20 ng.kg(-1).min(-1) ANG II to clamp ANG II at high levels (ANG-Hi, n = 10). Rats ingested a 0.4% NaCl diet for 3 days and then a 4.0% NaCl diet for 11 days. Arterial pressure of rats fed the 0.4% NaCl diet was lower in ANG-Lo (84 +/- 2 mmHg) compared with Con (101 +/- 3 mmHg) and ANG-Norm (98 +/- 4 mmHg) groups, whereas ANG-Hi rats were hypertensive (145 +/- 4 mmHg). Salt sensitivity was expressed as the change in arterial pressure divided by the change in sodium intake on the last day of the 4.0% NaCl diet. Salt sensitivity (in mmHg/meq Na) was lowest in Con rats (0.0 +/- 0.1) and progressed from ANG-Lo (0.8 +/- 0.2) to ANG-Norm (1.5 +/- 0.5) to ANG-Hi (3.5 +/- 0.5) rats. We conclude that the major determinant of salt sensitivity of arterial pressure is the basal level of plasma ANG II rather than the responsiveness of the renin-angiotensin system.