A. Tejedor

Primary Renal Lymphoma: Report of 3 Cases and Review of the Literature

Primary renal lymphoma is a controversial entity. Only 29 cases have been reported since 1980. Diagnostic criteria are not well established. We report here 3 new cases and review the literature. Primary renal lymphoma was considered on the basis of uni- or bilateral nonobstructive nephromegaly with or without renal failure. In all cases, the diagnosis was made after renal biopsy. Extrarenal abdominal involvement was excluded by imaging techniques. The role of staging laparotomy remains controversial. Chemotherapy is the treatment of choice, but the prognosis is poor. We propose a clinical definition of primary renal lymphoma in order to achieve a better management of the disease.

Hypoxemia During Hemodialysis: A Critical Review of the Facts

The literature describing the fall in PaO2 during dialysis is intensively and critically reviewed. This phenomenon is related to both the type of membrane used (cellulosic v noncellulosic membrane), and to the composition of the dialysate (acetate v bicarbonate). It appears that a ventilation/perfusion mismatch due to pulmonary leukostasis can, in part, explain hypoxemia in patients dialyzed with cellulosic membranes. This phenomenon is especially apparent in patients with preexisting pulmonary abnormalities. However, hypoventilation remains the major cause of hypoxemia. This hypoventilation is mainly due to CO2 consumption during acetate metabolism (acetate dialysis), or alkalinization of the blood (bicarbonate dialysis). The metabolic consequences of acetate metabolism, and of bicarbonate and CO2 losses through the dialyzer are critically analyzed. The cause for the increment in oxygen consumption during acetate dialysis is examined. Finally, the respective role of these combined factors are described and used to explain the changes in VCO2, VO2, respiratory quotient (RQ), and PaO2 reported in the literature during dialysis against acetate and/or bicarbonate.

Fluorescence Measurement of Intracellular pH on Proximal Tubule Suspensions

BCECF is used for intracellular pH (pHi) measurement in microperfused tubules. In this case, the perfusate washes out all BCECF leaking from the cells away from the optical light path. We have explored the use of BCECF for pHi determination on suspensions of dog renal proximal tubules (Percoll). This raises specific problems due to the accumulation of BCECF in the extracellular compartment generated by desesterification of BCECF-AM during loading and to leaking of BCECF into the extracellular medium occurring during the waiting time and during the measurement procedure. Repeated washing of the suspension reduced in part this contamination but did not eliminate the continuous leakage of BCECF: the specific intracellular signal is progressively reduced. We have examined the use of anion exchange resin (Dowex 1X-8, 200-400 mesh, Cl- form) to bind the extracellular BCECF (negatively charged). Dowex beads glued to one wall of the cuvette out of the optical path constitute an optically neutral sink removing BCECF as it leaks out of the cells. Using this technique, we had estimated the pHi of dog proximal tubule to 7.374 +/- 0.032 at extracellular pH of 7.325 +/- 0.021. The cellular pH is acutely, but transiently, alkalinized by NH4Cl and acidified by Na acetate. The BCECF signal was calibrated using nigericin. This technique improves significantly the measurement of pHi by BCECF fluorescence in tissue suspensions.

Glucose Metabolism in Dog Inner Medullary Collecting Ducts

The adenosine triphosphate (ATP) generating pathways of dog inner medullary collecting ducts (IMCD) were examined in vitro using suspensions of dog IMCD tubules incubated under aerobic and anaerobic conditions. Glucose is always the preferred substrate for this tissue, even if lactate can be oxidized under aerobic conditions. The metabolism of glucose proceeds largely towards lactate accumulation in the presence or absence of oxygen. Glycogen is also consumed and more markedly so during anoxia. The pentose shunt represents a minor pathway for glucose metabolism in this tissue. Under aerobic conditions, the net oxidation of glucose to CO2 contributes significantly to the cell energetics, mitochondrial and cytoplasmic mechanisms sharing equally the ATP synthesis. In the absence of oxygen, only the cytoplasmic routes of ATP synthesis are used, but the apparent ATP turnover is markedly reduced. A marked inhibition of the activity of the Na-K-ATPase during anoxia explains this observation. The utilization of glucose for osmolyte synthesis is a minor process and appears to be suppressed under anaerobic conditions. It is concluded that the ATP turnover is low in dog IMCD cells as compared with that of other nephron segments and is largely dependent upon glucose availability under aerobic or anaerobic conditions.

Cross-Talk between the Na+-K+-ATPase and the H+-ATPase in Proximal Tubules in Suspension

The cellular energy required for the activity of the Na(+)-K(+)-ATPase and of the H(+)-ATPase was estimated in intact proximal tubules in suspension. Both the fall in oxygen consumption (directly measured) and NADH oxidation (as estimated from exogenous substrate metabolism) were measured before and following application of ouabain (1 mM) to inhibit the sodium pump, following bafilomycin (0.1 mM) to inhibit the proton pump or following a combination of these inhibitors. The data demonstrate that the sodium pump utilizes 43% and the proton pump 19% of the phosphorylating NADH turnover of canine proximal tubules studied in vitro. However, a significant and stoichiometric stimulation of one pump was observed upon inhibition of the other. The NADH turnover related to the sodium pump increased from 308 to 402 (delta = 94) mumol.g-1 wet weight.h-1 following bafilomycin application and that of the proton pump from 136 to 230 (delta = 94) following ouabain application. This stimulation was largely abolished by inhibition of the Na+/H+ exchange occurring in either direction by amiloride or methylisobutylamiloride. It is concluded that a cross-talk occurs between the basolateral sodium pumps and the proton pumps located on the brush border membrane and/or on endosomes in proximal tubules. This cross-talk appears to be mediated by Na+/H+ exchange suggesting that both the proton pump and the Na+/H+ exchanger may contribute in a cooperative fashion to the proximal secretion of protons.

Substrate-induced modulation of ATP turnover in dog and rabbit proximal tubules

SummaryIn dog proximal tubules in suspension, the addition of glucose increased significantly the ouabain-sensitive fraction of respiration, a response suppressed by phlorizin. The addition of α-methyl-d-glucoside (α-MG) had a modest effect and 3-O-methyl-d-glucoside (3-O-MG) had no effect. The different stimulation of the Na+,K+-ATPase activity elicited for each hexose could be explained by a different increment of net transepithelial flux of sodium induced by the sodium: hexose cotransport. This flux is a direct function of the transport characteristics of both luminal and antiluminal membranes of proximal cells for these sugars: glucose is rapidly transported by both membranes (allowing a large transepithelial flux of glucose: sodium) while αMG is poorly transported by the basolateral, and 3-O-MG by the luminal, membrane of the dog proximal tubule (allowing a small transepithelial flux of hexoses and sodium). However the overall tubular respiration of dog proximal tubules was not increased by glucose addition because the increment in the ouabain-sensitive fraction was accompanied by a reciprocal decrement in an ouabain-insensitive but oligomycin-or N′,N′ dicyclohexylcarbodiimide (DCCD)-sensitive (or in the bafilomycin-sensitive) component of respiration. This component reflects the activity of a large BBM-bound H+-ATPase found in this species. The intracellular pH of dog proximal tubules in suspension was measured using the proton-sensitive fluorescent probe 2′,7′-bis-2-(carboxyethyl)-5, (and 6)-carboxyfluorescein. Glucose application significantly alkalinized the cells. In contrast, other substrates such as lactate or acetate simultaneously acidified the cells and increased the ouabain-insensitive phosphorylative respiration of dog tubules. These observations suggest that a modulation of the activities of both the sodium and most probably the proton pump is elicited by substrate availability in suspensions of proximal tubules.