The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial.

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

Animal models of renal disease.

Mice have become a favored species to model disease. Many mouse strains have proven relatively resistant to some manipulations that have generated renal disease in other species. Kirchhoff et al. describe a means of producing hypertension, proteinuria, and glomerular sclerosis in a mouse strain.

Downloadable computer models for renal replacement therapy.

Mathematical models can predict solute clearances and solute concentrations during renal replacement therapy. At present, however, most nephrologists cannot use these models because they require mathematical software. In this report, we describe models of solute transport by convection and diffusion adapted to run on the commonly available software program Excel for Macintosh computers and PCs running Windows. Two programs have been created that can be downloaded from http://www.stanford.edu/~twmeyer/ or http://dev.satellitehealth.com/research/journal.asp. The first, called 'Dr Addis Clearance Calculator', calculates clearance values from inputs including the blood flow Q(b), the hematocrit, the ultrafiltration rate Q(f), the dialysate flow rate Q(d), the reflection coefficient sigma and the mass transfer area coefficient K(o)A for the solute of interest, and the free fraction f if the solute is protein bound. Solute concentration profiles along the length of the artificial kidney are displayed graphically. The second program, called 'Dr Coplon Dialysis Simulator', calculates plasma solute concentrations from the clearance values obtained by the first program and from additional input values including the number of treatments per week, the duration of the treatments, and the solute's production rate and volumes of distribution. The program calculates the time-averaged solute concentration and provides a graphic display of the solute concentration profile through a week-long interval.

The development of clearance methods for measurement of glomerular filtration and tubular reabsorption.

This essay looks at the historical significance of four APS classic papers that are freely available online: Jolliffe N, Shannon JA, and Smith HW. The excretion of urine in the dog. III. The use of non-metabolized sugars in the measurement of the glomerular filtrate. Am J Physiol 100: 301-312, 1932 (http://ajplegacy.physiology.org/cgi/reprint/100/2/301). Shannon JA. The excretion of inulin by the dog. Am J Physiol 112: 405-413, 1935 (http://ajplegacy.physiology.org/cgi/reprint/112/3/405). Shannon JA and Fisher S. The renal tubular reabsorption of glucose in the normal dog. Am J Physiol 122: 765-774, 1938 (http://ajplegacy.physiology.org/cgi/reprint/122/3/765). Shannon JA, Farber S, and Troast L. The measurement of glucose Tm in the normal dog. Am J Physiol 133: 752-761, 1941 (http://ajplegacy.physiology.org/cgi/reprint/133/3/752).

Aldosterone in progressive renal disease.

Blockade of the renin-angiotensin-aldosterone system has proven effective in retarding progression of renal disease in the remnant kidney model, as well as other experimental diseases, and, most importantly, in a range of progressive human renal diseases. Attention has focused on the role of angiotensin II (Ang II) in propagating progression both by its hemodynamic and nonhemodynamic actions. Recent evidence, predominately in the remnant kidney model, indicates that the drugs used to block this hormone system, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, also lower aldosterone levels. Thus, aldosterone, as well as angiotensin II, appears to be instrumental in sustaining the hypertension and fibroproliferative destruction of the residual kidney.

Aldosterone in renal disease.

Blockade of the renin-angiotensin-aldosterone system has proved effective in retarding the progression of renal disease in the remnant kidney model, as well as other experimental diseases, and most importantly, in a range of progressive human renal diseases. Attention has focused on the role of angiotensin II in propagating progression both by its hemodynamic and non-hemodynamic actions. Recent evidence, predominantly in the remnant kidney model, indicates that the drugs used to block this hormone system, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, also lower aldosterone levels. Aldosterone as well as angiotensin II thus appears to be instrumental in sustaining the hypertension and fibroproliferative destruction of the residual kidney.

The course of the remnant kidney model in mice.

The remnant kidney model was produced in mice by unilateral nephrectomy and partial infarction of the remaining kidney. Control mice underwent laparotomy only. The mice were studied for up to 44 weeks. No quantitative differences were noted in systolic arterial pressure, proteinuria, or histopathology between control mice and those with a remnant kidney. Glomerular enlargement occurred in the remnant kidney.

The renin-aldosterone axis in two models of reduced renal mass in the rat.

The renin-angiotensin-aldosterone system participates in chronic progressive renal disease. The studies presented here assessed the importance of aldosterone in two different methods of reduced kidney mass in the rat, i.e., the infarction model (INF; uninephrectomy plus infarction of approximately two-thirds of the other kidney) and surgical excision or polectomy (POL; uninephrectomy plus surgical excision of both poles of the other kidney). Equivalent degrees of reduction in renal mass were confirmed by the similarity of serum creatinines 3 d after the ablative procedure. Measurements were made thereafter at 2 and 4 wk postablation. Systolic arterial pressure was greater with INF at both 2 and 4 wk. Proteinuria was also greater in the INF group at both time periods. The percentage of glomeruli with sclerosis measured at 4 wk tended to be greater in the INF group; however, this difference was not of statistical significance. At 2 wk, plasma renin activity and plasma aldosterone levels were lower in the POL group. The renin concentration in the scar region of the kidneys in the INF group was higher than in the kidney of the POL group. In conjunction with the lower plasma aldosterone, rats in the POL group had higher plasma potassium concentrations at 2 wk. In summary, higher aldosterone and plasma renin levels distinguish the INF model from the POL and likely contribute to the greater proteinuria and hypertension in the INF model.

Interaction of angiotensin II and TGF-beta 1 in the rat remnant kidney.

An interaction between angiotensin (Ang) II and transforming growth factor (TGF)-beta 1 is gaining increasing recognition. Ang II has been implicated in the progression of renal disease, and TGF-beta 1 is a potent fibrosis-promoting cytokine. We sought to determine whether the beneficial effects of renin-angiotensin system blockade on remnant kidney function were associated with a reduction in renal TGF-beta 1 in this model of chronic renal failure. After subtotal renal ablation, rats fed a 40% protein diet and treated with losartan not only had a reduction in systolic BP (96 +/- 8 versus 130 +/- 8 mmHg, P < 0.05, losartan versus control) and urinary protein excretion (4 +/- 5 versus 23 +/- 20 g/d, P < 0.05, losartan versus control), but also exhibited a reduction in renal TGF-beta 1 mRNA (194 +/- 64 versus 411 +/- 101 optical density units, P < 0.05, losartan versus control) and TGF-beta 1 protein levels (9.8 +/- 2.5 versus 18.6 +/- 5.8 ng/g of renal tissue, P < 0.05, losartan versus control). The elevation of TGF-beta 1 in the remnant kidney was most pronounced in the scar region (22.9 +/- 13.1 versus 5.8 +/- 3.7 ng/g, P < 0.05, scar versus nonscar). A combination of reserpine, hydralazine, and hydrochlorothiazide, although effective in lowering systemic BP in this model of chronic renal failure, was not associated with a reduction in proteinuria or TGF-beta 1. We conclude that in this model of progressive renal injury, Ang II antagonism may exert a beneficial effect in part by its negative influence on TGF-beta 1.

Role of the renin-angiotensin-aldosterone system in the progression of renal disease: a critical review.

Interruption of the renin-angiotensin-aldosterone system (RAAS) by converting enzyme inhibition or angiotensin II (ANG II) receptor antagonism dramatically reduces injury in the remnant kidney model. Furthermore, converting enzyme inhibition reduces proteinuria and slows the decline in renal function in clinical disease. Hemodynamic actions of ANG II in the kidney in conjunction with a more poorly defined effect of the RAAS on systemic hypertension have been posited as the major mechanisms for maintenance of elevated glomerular pressure. Reductions in glomerular pressure have been attributed, at least in part, to removal of intrarenal effects of ANG II. Growth and fibrotic actions of ANG II may also contribute to progressive renal injury and relief from them reduce injury. The participation of circulating aldosterone in the remnant kidney model has been recently raised. Hyperaldosteronism and adrenal hypertrophy attend the hypertension, proteinuria, and glomerulosclerosis of this model. Although the hemodynamic actions of aldosterone probably account for some of the adverse effects it has in this model, other direct cellular actions may participate in its renal, as well as cardiac and fibrotic consequences. Thus, the RAAS, working through both ANG II and aldosterone, contributes to chronic progressive renal injury.

The renal hemodynamic basis of diabetic nephropathy.

Diabetic nephropathy occurs in approximately one third of individuals with insulin-dependent diabetes mellitus (IDDM), recent studies suggest that a similar proportion of non-insulin-dependent diabetes mellitus (NIDDM) patients develop this serious complication as well. Of the many risk factors identified in the pathogenesis of nephropathy, hemodynamic alterations have been particularly well studied. Increases in glomerular filtration rate (GFR), largely driven by increases in plasma flow and glomerular capillary pressure, are apparent in early IDDM and NIDDM. Furthermore, the elevation in capillary pressure may be damaging to glomerular endothelial, epithelial and mesangial cells, thereby initiating and contributing to the progression of diabetic nephropathy. Numerous mediators of diabetic hyperfiltration have been proposed, and this phenomenon likely reflects a mutilfactorial etiology. The purpose of this article is to examine the hemodynamic alterations characteristic of diabetic nephropathy, their etiology, and their role in the development and progression of diabetic nephropathy.

Aldosterone is a major factor in the progression of renal disease.

There is compelling evidence supporting the renin-angiotensin-aldosterone system contribution in experimental and human renal disease. Interruption of this system by converting enzyme inhibition or angiotensin II receptor antagonism reduces injury. Angiotensin II contributes to the progression of renal disease through its direct vascular effects and proliferative properties. The mediators of angiotensin II induced renal injury are many and include TGF-beta, PDGF, bFGF, and endothelin. Though the mechanisms involved in its contribution to progressive renal disease are not well delineated, aldosterone seems to be an overlooked contributor to the progression of kidney disease and its effects may also depend on both its hemodynamic and more direct cellular actions.

Role of aldosterone in the remnant kidney model in the rat.

The renin-angiotensin-aldosterone system (RAAS) participates in the injury sustained by the remnant kidney. Our studies assessed the importance of aldosterone in that model and the response of aldosterone to drugs interfering with the RAAS. Initially, four groups of rats were studied: SHAM-operated rats, untreated remnant rats (REM), REM rats treated with losartan and enalapril (REM AIIA), and REM AIIA rats infused with exogenous aldosterone (REM AIIA + ALDO). The last group was maintained with aldosterone levels comparable to those in untreated REM rats by constant infusion of exogenous aldosterone. REM rats had larger adrenal glands and a > 10-fold elevation in plasma aldosterone compared to SHAM. REM AIIA rats demonstrated significant suppression of the hyperaldosteronism as well as marked attenuation of proteinuria, hypertension, and glomerulosclerosis compared to REM. REM AIIA + ALDO rats manifested greater proteinuria, hypertension, and glomerulosclerosis than REM AIIA rats. Indeed, by 4 wk of observation all of these features of the experimental disease were similar in magnitude in REM AIIA + ALDO and untreated REM. In separate REM rats spironolactone administration did not reduce glomerular sclerosis but did transiently reduce proteinuria, lowered arterial pressure, and lessened cardiac hypertrophy. In summary, aldosterone contributes to hypertension and renal injury in the remnant kidney model.

Learning the "numbers game" of today's contact lens fitting: clinical and business pearls.

A "chair time model" for contact lens pricing is a valuable administrative tool. Relative sagittal depth is an easy comparison to use when evaluating the theoretical fit of one soft lens versus another. Biological oxygen apparent transmissibility (BOAT) and a calculated value of oxygen transmissibility (Dk/L) are two totally different assessments and the significance of BOAT will need to be clinically tested over time.