Structure-function relationships in aquaporins.

The identification of members of the aquaporin family as the primary water channels of cell membranes has been followed up by an intense effort to determine how these channels work. Specifically, investigators have sought to learn why these channels are selective for water and how they exclude proton trafficking. Molecular-dynamics studies using elegant, extremely detailed computer models based on accurate crystallographic maps of the channels show the basis for the selectivity of the channel. Channel size, the location of hydrophobic amino-acid side chains, and specific interactions of water dipoles with a charged residue near the most constricted point of the channel indicate that water molecules travel in single file through the center of the channel, and that the orientation of water molecules is manipulated to prevent the formation of a water wire spanning the channel. Finally, the number of water molecules calculated to be aligned in single file in the channel constriction fits predictions based on classic studies of the osmotic permeability: diffusive permeability ratios in water-permeable membranes.

Metabolic alkalosis, bedside and bench.

Although significant contributions to the understanding of metabolic alkalosis have been made recently, much of our knowledge rests on data from clearance studies performed in humans and animals many years ago. This article reviews the contributions of these studies, as well as more recent work relating to the control of renal acid-base transport by mineralocorticoid hormones, angiotensin, endothelin, nitric oxide, and potassium balance. Finally, clinical aspects of metabolic alkalosis are considered.

Antineutrophil Cytoplasmic Antibodies-Negative Pauci-Immune Crescentic Glomerulonephritis Associated with Multiple Myeloma.

Pauci-immune crescentic glomerulonephritis (PICGN) is most commonly associated with antineutrophil cytoplasmic antibodies (ANCA). We report a case of chronic, sclerosing ANCA-negative PICGN discovered when a patient presented with multiple myeloma. A 57-year-old woman presented with complaints of nausea, emesis and weakness. She was found to be in renal failure with a serum creatinine of 9.4 mg/dl, mild hyperkalemia and acidosis. She was noted to have normochromic, normocytic anemia with normal platelet and white cell counts, normal plasma proteins and serum protein electrophoresis. Further studies revealed increased concentrations of κ and λ light chains in a ratio of 34.89; a bone marrow biopsy found 12% plasma cells. Serum protein electrophoresis revealed no spike. ANCA, anti-glomerular basement membrane, antineutrophil antibody, hepatitis panel and serum complements were normal. A kidney biopsy result showed chronic sclerosing PICGN plus tubular necrosis, severe tubular atrophy, interstitial fibrosis and severe arteriosclerosis. Congo red stains were negative and electron microscopy showed no intraglomerular deposits. The patient was subsequently treated for myeloma with bortezomib and dexamethasone with good hematologic response but never recovered renal function. She remains on outpatient hemodialysis. Renal manifestations of myeloma often involve glomerular deposition disease, tubulointerstitial disease, with characteristic proteinaceous casts, or both. In contrast, our patient demonstrated neither of these findings but had chronic sclerosing PICGN. Crescentic glomerulonephritis occurring in patients with plasma cell dyscrasias has been previously reported, but the association remains extremely rare.

Carcinoma of the lungs causing enlarged kidneys.

Bilateral enlarged kidneys can be caused by a number of conditions. Renal metastasis is included in the differential diagnosis. We report a case of a 67-year-old woman with a 6-month history of productive cough and unintentional weight loss. Cavitary pulmonary lesions and bilateral enlarged kidneys were noted on imaging studies. Hematuria, azotemia, and proteinuria were present. Renal biopsy showed squamous carcinoma cells invading normal-appearing glomeruli and atrophic tubules. The invasive squamous cells stained negative for CK7 and CK 20. Lung biopsy confirmed squamous cell carcinoma. Our case shows that in patients with renal enlargement, even with the absence of a focal mass, renal metastasis should be considered, especially in those with suspected or diagnosed malignancy elsewhere.

Outcomes research in dialysis.

Worldwide, the number of patients with end stage renal disease (ESRD) and the number of ESRD patients receiving renal replacement therapy is growing. In the United States the number of patients enrolled in the Medicare-funded ESRD program has grown substantially, from approximately 10000 beneficiaries in 1973 to 340261 as of December 31, 1999. United States has the highest incidence ESRD of 317 per million population. Despite the magnitude of resources committed to the treatment of ESRD and the substantial improvements in the quality of dialysis therapy, these patients continue to experience significant mortality and morbidity, and reduced quality of life. Moreover, 50% of dialysis patients have 3 or more comorbid conditions, the mean number of hospital days per year is approximately 14 per patient, and self reported quality of life is far lower in dialysis patients than in general population. The most desirable interventions are those that specifically target measurable global outcomes such as mortality, morbidity, and health care costs. Nevertheless, patient outcomes that have shown links with these global outcomes may also be appropriate targets for intervention. This article will briefly review the available literature to discuss the role of important clinical indicators on dialysis outcomes and their impact on continuing care of ESRD population.

Sirolimus induced granulomatous interstitial pneumonitis.

OBJECTIVES: Report a case of sirolimus induced granulomatous pneumonitis. BACKGROUND: Sirolimus is used in clinical transplantation as an immunosuppressive agent. Pulmonary toxicity does occur, but only a few cases of sirolimus associated granulomatous interstitial pneumonitis have been reported. METHODS: Case report and literature review. RESULTS: This 53-year-old woman with ESRD from polycystic kidney disease status post deceased donor kidney transplantation presented with fever, progressive dyspnea, and hypoxia for two weeks. She had been switched to sirolimus two months before admission. A CT scan of the chest revealed bilateral ill-defined patchy ground glass opacities. Extensive investigations were negative for infection. Video-assisted thoracoscopic biopsy showed granulomatous interstitial pneumonitis. Her symptoms and infiltrates resolved after sirolimus discontinuation and corticosteroid treatment. CONCLUSIONS: Drugs induced pneumonitis should always be considered in transplant patients after infectious or other etiologies have been excluded. Sirolimus can cause granulomatous infiltrates in the lung possibly secondary to T-cell mediated hypersensitivity.