Charles S. Brooks

Clinical Appraisal of Creatinine Clearance as a Measurement of Glomerular Filtration Rate

The plasma creatinine and the endogenous creatinine clearances are two of the most commonly used tests in clinical medicine to assess glomerular filtration rate. However, the contribution that tubular secretion of creatinine has on the total endogenous creatinine clearance (Ccr) is not generally known, nor are the effects renal insufficiency has on the tubular secretion of creatinine. To assess the above, 123 human subjects, with a wide range of renal function, underwent simultaneous Ccr and inulin clearances (Cin). The results indicate that: (1) Ccr approximates Cin only when Cin is normal; (2) a normal plasma creatinine of Ccr is not measurable evidence of a normal Cin; and (3) with progressive decline in Cin, there is progressive increase in the tubular secretion of creatinine, leading to a progressive disparity between Ccr and Cin.

The long-term effect of propranolol therapy on renal function

Abstract It has been reported that the intravenous administration of beta blocking agents reduces renal plasma flow and glomerular filtration rate from 10 to 20 per cent. In contrast, little is known about the chronic effects of these agents on renal function when given orally. To assess this question, eight normal subjects underwent timed true and regular creatinine clearances (C cr ), inulin clearances (C in ) and para-amino hippurate clearances (C PAH ) after sequential weeks of therapy with 0, 80, 160, 240 and 320 mg of propranolol/day. Weight, blood pressure and heart rate were measured on each visit. Compliance was tested and confirmed by monitoring plasma propranolol concentrations. The results indicate that the use of propranolol in normal man significantly reduces C in (27 per cent) and C PAH (26 per cent). Such decreases are probably, in part, due to reductions in cardiac output, as suggested by reductions in systolic blood pressure and heart rate. Furthermore, there was a sustained reduction in C in following the withdrawal of propranolol therapy. C cr technics did not reflect the magnitude of the reduction in glomerular filtration rate. The fractional excretion of creatinine demonstrated a significant inverse relationship to C in , suggesting that creatinine secretion is increased with propranolol. We conclude that propranolol therapy results in prolonged changes in glomerular filtration rate, which may not revert to normal following its withdrawal.

Renal Function Studies in Man With Advanced Renal Insufficiency

In subjects with advanced renal insufficiency, the average of the creatinine and urea clearances ([Ccr + Cur]/2) is frequently used as an indicator of glomerular filtration rate (GFR). To test the accuracy of this method, 31 subjects with inulin clearance (Cin) less than 20 ml/min/1.73 m2 underwent simultaneously timed creatinine, urea, and inulin clearances. The results indicated that: (1) Ccr correlated positively with Cin; mean fractional excretion of creatinine (Ccr/Cin) was 1.5; (2) Cur correlated positively with Cin; in contrast to creatinine, the fractional excretion of urea (Cur/Cin) correlated negatively with Cin; (3) in 10 of 12 subjects with Cin less than 8 ml/min 1.73 m2, the Cur/Cin was greater than 1, suggesting that tubular secretion may have occurred; and (4) the (Ccr + Cur)/2 correlated positively with Cin and was the best clinical indicator of GFR.

Nutrition in Renal Transplantation

This study was conducted to determine whether a high-nitrogen, low-carbohydrate diet in the immediate post-operative renal transplant period could result in a positive nitrogen balance and fewer cushingoid side effects. Twelve consecutive nondiabetic renal transplant recipients were randomly assigned to the isocaloric control or experimental diet group. The six patients ingesting the experimental diet achieved positive nitrogen balance whereas five of the six patients on the control diet had a negative nitrogen balance. The nitrogen balance varied directly and proportionately with the protein intake. Potassium balance mirrored the nitrogen balance data. Cushingoid side effects did not develop in any of the six experimental diet patients whereas four of the six control diet patients had evidence of severe cushingoid appearance and two had moderate cushingoid appearance (P = .01). Based upon the findings of this study, we suggest that the renal transplant recipients diet could be altered to provide more protein and less carbohydrate to improve nitrogen balance and prevent cushingoid features. It is possible that a high-protein, low-carbohydrate diet may be used by additional patients taking steroids for other disease states to prevent cushingoid side effects and improve nitrogen balance.

Effects of diuretic and propranolol on plasma lipoprotein lipids

Ticrynafen (TCNF), a nonthiazide diuretic, has been reported to be nonhyperlipidemic. To define the effects of these drugs on plasma lipoproteins, experiments were performed in hypertensive subjects after placebo therapy, 4 wk after therapy with either hydrochlorothiazide (HCTZ) or TCNF, 3 mo after diuretic with propranolol, and 1 mo after therapy with propranolol alone. Plasma lipoproteins were separated by ultracentrifugation and the lipid fractions isolated by extraction and silicic acid thin‐layer chromatography. Plasma low‐density lipoprotein (LDL) total cholesterol fell and high‐density lipoprotein (HDL) total cholesterol rose in subjects receiving TCNF. TCNF had no effect on plasma very low‐density lipoprotein (VLDL) triglyceride or phospholipid. There were no significant changes in LDL or HDL total cholesterol in subjects on HCTZ. HCTZ tended to increase plasma VLDL triglyceride and phospholipid. The addition of propranolol to either diuretic had no effect on LDL or HDL total cholesterol but increased VLDL triglyceride, especially in subjects on HCTZ. Propranolol alone had no effect on any of the lipids measured.

Volume studies in men with mild to moderate hypertension.

The importance of salt and water in the pathophysiology of the hypertensive state is well recognized. The current study is the first to report simultaneous measurements of red blood cell mass, plasma volume, extracellular fluid and total body water levels. Studies were performed in 82 white men, 14 with normal blood pressure and 16 with low renin and 52 with normal renin hypertension. The results indicate that subjects with normal renin hypertension compared with age-matched controls are characterized by an absolute increase (1.5 liter/m2) in intracellular fluid (total body water minus extracellular fluid). Furthermore, the ratio of extracellular fluid to total body water is decreased (0.43 to 0.38). No volume differences were found between subjects with low renin hypertension and age-matched subjects with normal renin hypertension. We conclude that subjects with normal renin hypertension compared with age-matched peers are characterized by an expanded intracellular fluid and that subjects with low renin hypertension do not exhibit a unique volume disorder.

Sweet syndrome associated with furosemide

This case report describes a case of Sweet syndrome (SS) related to use of furosemide in a 46-year-old female who was admitted for treatment of congestive heart failure. Three days after administration of furosemide, the patient had a fever and a skin eruption appeared on her wrists, forearms, and legs. Biopsy of the skin lesion was consistent with SS. Infection was thought to be unlikely because of negative blood cultures, echocardiography, and other imaging studies. Careful review of her medications revealed that the patient received furosemide before the appearance of the skin eruption and fever. After discontinuation of furosemide, the patients skin lesion and fever resolved. A MEDLINE search from June 1966 to May 2004 revealed only one reference documenting the association of SS with furosemide administration. Patients who have development of SS without an obvious cause should have their medication list closely reviewed.

Comparative Effects of Ticrynafen and Hydrochlorothiazide on Blood Pressure, Renal Function, Serum Uric Acid and Electrolytes, and Body Fluid Spaces in Hypertensive Man

25 hypertensive subjects underwent a double-blind, randomized study to compare the effects of ticrynafen (TCNF) with hydrochlorothiazide (HCTZ) on blood pressure (BP), renal function, serum uric acid (UA) and electrolytes, and body fluid spaces. BP was similarly lowered by TCNF and HCTZ. Neither TCNF nor HCTZ had a significant effect on true or regular creatinine, inulin, or PAH clearances. TCNF lowered UA, whereas HCTZ elevated UA. Both produced similar electrolyte disturbances. Neither TCNF nor HCTZ, according to our methods, had a significant effect on plasma volume, extracellular fluid, or total body water. The primary advantage of TCNF compared with HCTZ is its profound hypouricemic effect.

Systemic Mastocytosis Associated With Membranous Nephropathy and Peripheral Neuropathy

A report of the occurrence of membranous nephropathy and peripheral neuropathy in a patient with systemic mastocytosis is presented. Previous reviews of patients with systemic mastocytosis have not noted this association. During cyclical therapy with prednisone and chlorambucil in this case, nephrotic-range proteinuria remitted. Peripheral neuropathy resolved 10 months after discontinuation of therapy. Pathophysiological mechanisms resulting in this clinical presentation may be immunologically mediated.