IT is now more than 30 years since Addis suggested that protein intake be restricted in patients with chronic renal insufficiency.1 His aim was not to reduce uremic symptoms but rather to prevent a...

Dietary Protein Intake and the Progressive Nature of Kidney Disease: The Role of Hemodynamically Mediated Glomerular Injury in the Pathogenesis of Progressive Glomerular Sclerosis in Aging, Renal Ablation, and Intrinsic Renal Disease

Dendrimers are branched, synthetic polymers with layered architectures that show promise in several biomedical applications. By regulating dendrimer synthesis, it is possible to precisely manipulate both their molecular weight and chemical composition, thereby allowing predictable tuning of their biocompatibility and pharmacokinetics. Advances in our understanding of the role of molecular weight and architecture on the in vivo behavior of dendrimers, together with recent progress in the design of biodegradable chemistries, has enabled the application of these branched polymers as anti-viral drugs, tissue repair scaffolds, targeted carriers of chemotherapeutics and optical oxygen sensors. Before such products can reach the market, however, the field must not only address the cost of manufacture and quality control of pharmaceutical-grade materials, but also assess the long-term human and environmental health consequences of dendrimer exposure in vivo.

Designing dendrimers for biological applications.

Micropuncture studies were performed in three groups of male Munich-Wistar rats 1 wk after surgery: group I, eight control rats that underwent laparotomy and were fed a normal diet; group II, nine rats that underwent right nephrectomy and segmental infarction of five-sixths of the left kidney and were fed a normal diet; and group III, seven rats that underwent the same renal ablative procedure and were fed a low protein diet. Single nephron glomerular filtration rate (SNGFR) was higher in the remnant kidney of group II rats compared with group I rats due to higher average values for mean glomerular transcapillary hydraulic pressure difference (delta P) and initial glomerular plasma flow rate (QA) in group II. Glomeruli in remnant kidneys of group II showed striking alterations in morphology, including epithelial cell protein reabsorption droplets, foot process fusion, and mesangial expansion. Group III rats demonstrated a mean SNGFR not statistically different from that of group I, but significantly less than that of group II rats. This lack of absolute hyperfiltration in remnant glomeruli of group III rats relative to group I obtained because QA and delta P did not increase above values found in group I. The glomerular structural lesions seen in group II were also largely attenuated in group III. These studies demonstrate that alterations in glomerular hemodynamics associated with renal ablation are accompanied by structural lesions and suggest that sustained single nephron hyperfiltration may have maladaptive consequences by damaging remnant glomeruli.

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Hyperfiltration in remnant nephrons : A potentially adverse response to renal ablation

Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

Cell Biology of the Glomerular Podocyte

Fermentation of lignocellulosic hydrolysates. I: inhibition and detoxification

The immobilization of whole cells: Engineering principles

Permselectivity of the glomerular capillary wall: III. Restricted transport of polyanions

DEEN, W. M., C. R. ROBERTSON, AND B. M. BRENNER. A model of glomerular ultrajltration in the rat. Am. J. Physiol. 223(5) : 1178-l 183. 1972.-A mathematical model has been developed to investigate the influence of a number of physiological variables on the net driving pressure for ultrafiltration (PuF) in the rat glomerulus. The model was used to predict osmotic pressure differences as functions of distance along a glomerular capillary for a wide range of glomerular capillary plasma flow rates, membrane hydraulic permeabilities (k), and axial pressure drops; and these pressure profiles are consistent with recently reported experimental findings. When filtration pressure equilibrium is achieved, results obtained with the model indicate that estimates of PUF at the beginning and end of the glomerular capillary bed cannot be used to infer the correct magnitudes of the mean value of PUF or k in the normal rat. The results also indicate that changes in single-nephron glomerular filtration rate will vary in proportion to changes in plasma flow rate when filtration pressure equilibrium occurs.

A model of glomerular ultrafiltration in the rat

An interfacial stress rheometer has been constructed to study the rheology of Langmuir films subjected to time-dependent flows A magnetized rod resides at the air−water interface and is set into oscillation by applying a sinusoidal magnetic field gradient Analysis of the amplitude and phase of the resulting rod motion relative to the applied force allows the determination of the dynamic surface modulus, Gs*(ω), and measurement of the relative elastic and viscous contributions of the monolayer Measurements at 22 °C were conducted on eicosanol (C20) and mixtures of a rigid-rod polymer, phthalocyaninatopolysiloxane (PcPS), dispersed in eicosanol The surface pressure dependence of the rheology for eicosanol reveals the presence of a maximum in the loss modulus, Gs‘ ‘(ω), within the L2‘ phase at Π = 6 mN/m In the LSI phase at pressures above 15 mN/m, the monolayer is Newtonian and has a surface viscosity of 003 mN·s/m The mixtures of PcPS with eicosanol are known to have two-dimensional nematic behavior

Channing R. Robertson

Papers

The immobilization of whole cells: Engineering principles

Permselectivity of the glomerular capillary wall: III. Restricted transport of polyanions

A model of glomerular ultrafiltration in the rat

An Interfacial Stress Rheometer To Study Rheological Transitions in Monolayers at the Air-Water Interface

Permselectivity of the glomerular capillary wall to macromolecules. II. Experimental studies in rats using neutral dextran