Cidio Chaimovitz

Association Between Renal Injury and Reduced Interleukin-15 and Interleukin-15 Receptor Levels in Acute Kidney Injury

Interleukin (IL)-15 serves as a survival factor for a broad array of cells. Renal cells express both IL-15 and its receptor (IL-15R); however, the role of IL-15 in the kidney is yet to be determined. We examined IL-15 and IL-15R levels in sepsis-related renal injury, ischemia-reperfusion injury (IRI), and cisplatin-induced nephrotoxicity. To test the anti-apoptotic effect of IL-15, Bcl-2/Bax mRNA levels were assessed in kidneys of IL-15Ralpha(-/-) mice and in IL-15-stimulated renal epithelial cells (RECs). In addition, RECs were exposed to cisplatin and apoptosis was evaluated by TUNEL staining, caspase-3 activity, and cell cycle analysis. Intrarenal IL-15 levels decreased 24 h after initiation of all three examined pathologies by 5.8-fold (sepsis), 11-fold (IRI), and 23-fold (cisplatin-induced nephrotoxicity). Further experiments revealed that while addition of rIL-15 (1 ng/mL) to wild-type (WT) RECs increased Bcl-2/Bax ratio by 2-fold, kidneys of IL-15Ralpha(-/-) mice exhibited 4-fold lower Bcl-2/Bax ratio compared to WT mice. Accordingly, IL-15 lowered the apoptotic rate in cisplatin-treated cultured REC, and IL-15Ralpha(-/-) renal cells exhibited a higher rate of cisplatin-induced apoptosis. Furthermore, IL-15 levels negatively correlated with BUN of cisplatin-treated mice (R = -0.69, P = 0.003), suggesting that a decline in renal-derived IL-15 is detrimental to renal cell survival and kidney function during pathological stress.

Enhancement of 24,25-Dihydroxyvitamin D Levels in Patients Treated with Continuous Ambulatory Peritoneal Dialysis

We measured 24,25-dihydroxyvitamin D [24,25(OH)2D] levels in patients treated with chronic ambulatory peritoneal dialysis (CAPD), before and after receiving vitamin D2 or 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3). Vitamin D2 administration led to an increase in 25-hydroxyvitamin D (25-OH-D) and a concomitant rise in 24,25(OH)2D. No change was observed in 1,25-dihydroxyvitamin D [1,25(OH)2D]. Administration of 1 alpha-OH-D3 resulted in an increase in 1,25(OH)2D3, and a concomitant rise in 24,25(OH)2D, but no change in 25-OH-D3. Thus, 24,25(OH)2D levels may be increased in CAPD patients by raising 25-OH-D levels, or by raising 1,25(OH)2D3 levels. Since the latter enhances specifically the renal 24-hydroxylase enzyme, we conclude that this enzyme is present in CAPD patients with kidneys in situ, and may be stimulated by adequate 1,25(OH)2D3 levels. Thus, administration of 1 alpha-OH-D3 to CAPD patients with kidneys in situ seems to be sufficient to obtain normal levels of 1,25(OH)2D3 and 24,25(OH)2D3. However, anephric patients require vitamin D2 in addition as a source of 25-OH-D, the substrate for extrarenal production of 24,25(OH)2D.

Effect of Renal Denervation and a-Adrenergic Blockade on Sodium Excretion in Dogs with Chronic Ligation of the Common Bile Duct

Summary Chronic ligation of the common bile duct (CBDL) is dogs causes sodium retention and a blunted natriuretic response to extracellular volume expansion (ECVE). Since increased sympatho-adrenal activity plays an important role in other sodium retaining states, the present study was undertaken to evaluate the role of renal denervation and a-adrenergic blockade on the renal handling of sodium in dogs with CBDL. Both renal denervation and the infusion of dibenzyline into the renal artery produced a slight but significant increment in urinary sodium excretion, but these changes were not different from those observed after renal denervation in normal animals. Also, these procedures did not improve the response to saline infusion in dogs with CBDL. These data indicate that the sympatho-adrenal activity does not play an important role in the salt retaining state that follows chronic ligation of the common bile duct. Anne Harrington and Miriam Bick provided technical help and Mrs. Catherine Hoyt provided secretarial assistance.

Nephrotic Syndrome Associated with Transitional Cell Carcinoma of the Bladder

We describe the occurrence of a nephrotic syndrome in association with transitional cell carcinoma of the bladder. The proteinuria disappeared several weeks after removal of the tumor. Light and electron microscopy were compatible with a minimal-change lesion, but immunofluorescence showed linear immunoglobulin deposition. Immunoglobulins eluted from the tumor reacted specifically with the kidney and vice versa. We conclude that antibody formation against a specific component of basement membrane common to both kidney and tumor gave rise to the nephropathy in this case.

X-Ray Microanalysis of Uremic Nephrocalcinosis

The nature of uremic nephrocalcinosis was studied by means of X-ray microanalysis in 5/6 nephrectomized rats. The data show that calcified deposits in the renal parenchyma of uremic rats contained substantial amounts of calcium, magnesium, aluminum and silicon. Since calcificates did not reveal a uniform composition they were arbitrarily divided into 3 categories: high-calcium with Mg:Al:Si: Ca molar ratios 7:3:8:37; low-calcium particles were characterized by Fe:Mg:Al:Ca:Si molar ratios 7:3:5:6:13; while intermediate-calcium particles showed Al:Mg:Si:Ca molar ratios equivalent to 2:4:6:7. The variability of calcified deposits in the renal parenchyma of 5/6 nephrectomized rats might be due to different sources, different environmental conditions along the nephron and different stages of calcification process. It is suggested that aluminum and silicon content of deposits may be of value in further characterization of uremic nephrocalcinosis.