De novo minimal change disease.

Beyond the acute posttransplantation period, glomerular causes of proteinuria in the renal allograft include recurrent glomerulopathy, transplant-associated entities, and de novo disease. We present a case of de novo minimal change disease with reversible acute renal failure occurring 2.5 years posttransplantation in a 56-year-old man. The cause of end-stage renal disease in the native kidney was membranous glomerulopathy. De novo minimal change disease in the renal allograft is an extremely rare entity requiring stringent clinical-pathological criteria for diagnosis. Many of the cases previously reported as de novo minimal change disease fail to meet these criteria. We review the eight reported cases that appear to fulfill a strict definition of minimal change disease in the context of the current report.

Renal biopsy in patients 65 years of age or older. An analysis of the results of 334 biopsies.

We studied the clinical and pathological data for 334 patients age 65 or more who underwent renal biopsy for acute renal failure (ARF, n = 55), subacute renal failure (SRF, n = 72), chronic renal failure (CRF, n = 57), proteinuria (n = 137), and hematuria (n = 13). Tissue diagnoses were glomerulopathy (n = 252, 75.4%), acute tubular lesions (n = 18), interstitial nephritis (n = 23), vascular diseases (n = 36, including 14 with cholesterol emboli), and five miscellaneous diagnoses. Of the 55 patients with ARF, 23 had a glomerular lesion, 15 had acute tubular necrosis, and 8 had acute interstitial nephritis. Of 72 patients with SRF, 49 had a glomerulopathy, 12 had a vascular disorder, and six had acute interstitial nephritis. Hence, patients with ARF or SRF exhibited a high potential for reversible lesions. Only 11.3% of patients with CRF had potentially reversible causes. The most common causes of proteinuria were membranous glomerulopathy (34.3%), minimal change disease (14.6%), focal segmental sclerosis (11.7%), and amyloidosis (8.8%). Of the 25 patients with advanced nephrosclerosis, 24 had renal failure, 20 were hypertensive, and 13 had cholesterol emboli. Of 33 patients with diabetes mellitus, 66.7% were found to have lesions not related to diabetes. We conclude that renal biopsy is most useful in older patients with ARF or SRF because of potentially reversible renal disease. Old age alone is not a contraindication to performing a renal biopsy.

Comparison of the effects of sodium bicarbonate versus sodium citrate on renal acid excretion.

Citrate is used commonly as an alkalinizing agent and in the management of nephrolithiasis, but its quantitative effect on acid-base homeostasis, as judged by changes in renal net acid excretion, has not been delineated. We therefore administered 61 mEq of sodium citrate/day for 4 days to 10 normal volunteers and compared the results to those obtained in 10 normal subjects (4 of whom also participated in the citrate protocol) given 60 mEq/day for 4 days of sodium bicarbonate, the prototypical alkalinizing agent. We found that the sodium citrate group experienced an average reduction in net acid excretion (45.5 +/- 7.2 mEq/day) that was very similar to that (42.0 +/- 7.2 mEq/day) induced by the same amount of sodium bicarbonate. In both groups, the reduction in net acid excretion was equivalent to approximately 70% of the alkali administered. The latter appeared to relate to an average negative hydrogen ion balance of approximately 15 mEq/day, since there was an increase in blood [HCO3] in each group of about 2.5 mEq/l. We conclude that the findings demonstrate that the short-term effects of sodium citrate on acid-base homeostasis in normal subjects are indistinguishable from those of sodium bicarbonate.

Impairment of beta 2-adrenoceptor-stimulated potassium uptake in end-stage renal disease.

An abnormality of extrarenal mechanisms is believed to contribute importantly to the impaired potassium homeostasis in chronic renal failure. We evaluated the plasma potassium response to inhalation of albuterol, a beta 2 agonist, in eight patients who had end-stage renal disease and who were undergoing chronic hemodialysis and in eight control subjects. The purpose was to assess if an abnormality of the beta 2 adrenoceptor mechanism is present in uremia. The maximal decrement in plasma potassium concentration in the patients (0.12 +/- 0.04 mEq/L) was significantly less than that of the control subjects (0.30 +/- 0.05). Furthermore, the final plasma potassium concentration slightly exceeded baseline in the patients but was significantly reduced in controls, leading to the conclusion that an abnormal responsiveness of the beta 2 adrenoceptor may contribute to the impaired potassium tolerance found in patients who have end-stage renal disease.

Effect of routine doses of antacid on renal acidification.

Ten healthy volunteers took a magnesium and aluminium hydroxide antacid for 4 days, and their urinary acid excretion was measured. During antacid ingestion, blood bicarbonate levels did not change significantly, but there were highly significant rises in urine pH and bicarbonate excretion and falls in the 24 h excretion of titratable acid, ammonium, and net acid; the average change in net acid excretion was 41 +/- 4 mmol (72 +/- 9%) per 24 h. This large reduction in net acid excretion appears to result from neutralisation of more hydrochloric acid than sodium bicarbonate in the gastrointestinal tract rather than from absorption of exogenous alkali. Although metabolic alkalosis does not occur with their use in normal individuals, these antacids should not be termed "non-systemic". They might cause important changes in renal drug handling, solubility of excreted substances, or acid-base status in patients at risk.

Hepatic microsomal glucose-6-phosphatase of normal and alloxan-diabetic rats. Thermotropic effects on kinetics and interaction with deoxycholate and 1-anilino-8-naphthalene sulfonate.

Thermotropic effects on the kinetics of glucose-6-phosphatase (D-glucose-6-phosphate phosphohydrolase, EC 3.1.3.9) activity of hepatic microsomes from normal and alloxan-diabetic rat liver were investigated by determining V, Km and Ki (substrate inhibition) values. Influence of deoxycholate (0.1%) and 1-anilino-8-naphthalene sulfonate (2.5 mM) on the kinetics was also evaluated. 1. Substrate inhibition occurred at 0.06 M for the enzyme from normal rats and at 0.0-0.025 M for the enzyme from diabetic rats. 2. The enzyme from diabetic rats showed a transition that extended between 22.7 and 27 degrees C in the Arrhenius plot (log V vs. T-1) instead of at 19.5 degrees C. 3. Deoxycholate increased the V value of both enzymes without affecting substrate inhibition at all the temperatures but did not completely abolish the transition in the Arrhenius plot of the enzyme from diabetic rats. 4. 1-Anilino-8-naphthalene sulfonate eliminated substrate inhibition and activated the enzyme of normal rats above 27.5 degrees C by increasing both V and Km values. Below this temperature, the enzyme showed biphasic or allosteric kinetics. At low substrate concentrations it was activated as both V and Km values were increased. The enzyme from diabetic rats, on the other hand, was activated at all the temperatures and exhibited linear kinetics. 5. Binding of 1-anilino-8-naphthalene sulfonate to the microsomal fraction increased with decreasing temperature as revealed by the increase of relative fluorescence. The microsomal fraction of diabetic rats showed a more anomalous fluorescence response between 13-18 degrees C. 6. Enthalpy changes for glucose 6-phosphate binding to the inhibition site were slightly larger than binding to the active site. Calculated entropies of activation for transition state complex of glucose-6-phosphatase reaction were fairly large and negative. The free energy of activation (28-30 kcal/mol) was independent of temperature and experimental conditions. 7. In the microsomal fraction (total as well as rough), phospholipid content and fatty acid unsaturation index of phospholipids were decreased after diabetes. The level of free cholesterol remained unchanged but the molar ratio of cholesterol to phospholipid increased. The different thermal response and 1-anilino-8-naphthalene sulfonate interaction to the enzyme from diabetic rat and liver could be ascribed to the altered lipid environment of the enzyme on the endoplasmic reticulum membrane.