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M H De Keijzer

Publications and source records attributed to M H De Keijzer.

9 recordsLinked to original sources

Pathogenesis of glomerular injury in the fawn-hooded rat: effect of unilateral nephrectomy.

Fawn-hooded (FH) rats with congenital proteinuria and systemic and glomerular hypertension are very susceptible to renal damage at a young age. In this study, the effects of unilateral nephrectomy (UNX) on the function and structure of the remaining kidney in the FHH substrain were assessed. A long-term study was performed to determine the changes in systemic blood pressure, renal function, and proteinuria during the development of chronic renal failure in UNX-FHH and two-kidney (2K) FHH rats. Renal micropuncture and morphologic studies were performed at 4 wk after surgery. The long-term study showed that, after UNX, systolic blood pressure did not differ significantly (from that of 2K-FHH rats. After UNX, there was compensatory hyperfiltration, at about 70% of the 2K level, that could be maintained for 12 wk only. The subsequent fall in GFR was preceded by severe proteinuria. The mean survival time of UNX-FHH rats was only 35 wk. Micropuncture studies showed that the high mean glomerular capillary pressure of 2K-FHH rats was further elevated after UNX. The glomerular capillary ultrafiltration coefficient did not differ significantly between UNX-FHH and 2K-FHH rats. The weight of the remaining kidney and the mean glomerular tuft volume in UNX-FHH were, on average, 36 and 31% greater than in 2K rats. The results indicate that the FHH rat is extremely vulnerable to the adverse renal effects of UNX.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effect of protein intake and unilateral nephrectomy on renal function and eicosanoid excretion in rats.

Vasoactive eicosanoids may be involved in glomerular hyperfiltration following a high protein intake or removal of renal mass. We sequentially measured glomerular filtration rate (GFR), proteinuria (UpV), and urinary eicosanoid excretion in sham-operated (2K) and uninephrectomized (NX) rats on two diets. Compared with 12% protein (LP), 36% protein (HP) initially resulted in a higher GFR and UpV in both 2K and NX rats. Urinary excretion of 6kPGF1 alpha and TxB2 was higher on the HP diet. Ten weeks after NX, PGE2 excretion was slightly reduced, while that of TxB2 and 6kPgF1 alpha was the same as in 2K rats, indicating that the excretion per kidney had increased. From week 40, the GFR of NX rats on the HP decreased, preceded by a progressive increase in UpV. Excretion of PgE2, TxB2, and 6kPgF1 alpha was highest in the phase of proteinuric chronic renal failure. Thus, vasoactive eicosanoids are involved to maintain hyperfiltration induced by high protein intake or NX.

6-Ketoprostaglandin F1 alpha↗

The effect of protein intake on the lifelong changes in renal function of rats with a solitary kidney damaged at young age.

Changes in renal function were followed lifelong in male rats with only 1 kidney either intact or damaged by ureteral obstruction or ischemia. After surgery the rats were given a low (12%) or a high (36%) protein diet. After a period with a stable glomerular filtration rate, which was longer on the low protein diet, there was a linear decline in rats with an intact single kidney. The rate of decline was highest on the high protein diet, resulting in a shorter survival time. A decrease in urine osmolality and an increase in protein excretion preceded the decrease in filtration rate, while it was followed by an increase in blood pressure. The glomerular filtration rate of the rats with a single damaged kidney initially recovered to 75 to 80% of that of rats with an intact single kidney on the same diet. There was a linear decrease in the glomerular filtration rate, with the highest rate of decrease on the high protein diet. The mean survival time was less than that of rats with a single intact kidney. Proteinuria preceded the decrease in filtration rate, while hypertension was observed later. We conclude that in rats with a solitary kidney renal failure eventually develops. A low protein diet postpones and attenuates this development but it does not prevent it.

Albuminuria↗

Effects of dietary protein on the progression of renal failure in the Fawn-Hooded rat.

Fawn-Hooded (FH) rats on a normal protein intake develop focal glomerulosclerosis, proteinuria and hypertension and die prematurely because of renal failure. In the present study we examined the effect of a life long feeding of a low (12%)-protein (LP) diet and a high (36%)-protein (HP) diet on renal function, urinary protein excretion (UprotV), systolic blood pressure (SBP) and survival time. Compared to the LP diet, the HP diet initially raised the glomerular filtration rate (GFR) and the UprotV, while the SBP was about the same. The UprotV of rats on the HP diet increased steadily and the GFR started to decline after 40 weeks. The LP diet resulted in a prolonged period of stable renal function, limited proteinuria and an increased life span. In the 2nd year of life, the level of hypertension was less in FH rats on the HP diet. Throughout the study there was no relationship between the SBP and the UprotV. The low UprotV in FH rats on the LP diet points to a lower level of glomerular capillary pressure. The attenuated development of glomerular hypertension on the LP diet slows down the subsequent renal damage in FH rats. This is in agreement with the view that glomerular hypertension is an essential hemodynamic derangement responsible for progressive deterioration of glomerular function. As in other rat models, i.e. renal ablation or unilateral nephrectomy, the LP diet slowed down the development of renal failure but did not prevent it.

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Renal function in single-kidney rats.

Can a single kidney survive for a normal life span? This is the type of question frequently asked by patients and especially by parents of children who lose one kidney in early childhood. Based on our wide experience with single-kidney rats, we will try to give an answer to this question. After the removal of its counterpart, the single remaining kidney will rapidly adapt to the new situation by a compensatory increase in the glomerular filtration rate (GFR) and renal mass. This is true not only for intact kidneys but also for damaged ones. The GFR level obtained by damaged kidneys will be less than that of intact single kidneys, however, depending on the degree of initial damage. The GFR is stable for a certain period of time, which is longer for intact single kidneys than for damaged kidneys and also depends on the daily protein intake; after that renal function will deteriorate. This decline in GFR is preceded by a marked increase in urinary protein excretion. Although the follow-up period is not completed yet, the survival time of single intact kidneys in rats on a normal diet is expected to be 15%-20% less than the normal rat life span. In rats on a lifelong high protein intake the kidney survival time drops to 40% below the normal rat life span. In rats on a moderately reduced protein intake, however, single intact kidneys may survive for a normal life span. The situation is worse for single damaged kidneys. Depending on the severity of the initial damage, kidney survival time will be much less than a normal life span. We studied rats with an initial recovery to 75% of renal function. Despite this initial recovery, the animals died of renal failure within 50% of the expected life span. A low-protein diet prolonged the renal survival by about 12%, a high-protein diet shortened it by the same percentage.

Age Factors↗

Effect of protein intake on lifelong changes in renal function of rats unilaterally nephrectomized at young age.

Changes in glomerular filtration rate (GFR) and urinary protein excretion were determined during a lifelong follow-up period in male WAG/Rij rats, unilaterally nephrectomized (NX) just after weaning, and compared with changes in control rats with both kidneys intact (2K). After surgery, the animals were given either a low-protein (LP; 12%), normal-protein (NP; 24%) or high-protein (HP; 36%) diet. The GFR of 2K-rats was highest with the HP diet and lowest with the LP diet. With all three diets, the GFR of 2K rats remained stable for about 2 years. The mean survival time of 2K rats was not affected by the dietary protein intake and amounted to about 120 weeks. Initially, the GFR of NX rats was highest with the HP and lowest with the LP diet. The GFR remained stable for a period of 36 weeks with the HP diet, 48 weeks with the NP diet, and 72 weeks with the LP diet. Subsequently, the GFR fell linearly in the great majority of cases with all three diets. The highest rate of decline was found in NX rats given the HP diet. As a result, from week 72, the GFR of the NX rats on the LP diet was significantly higher than that of NX rats on either the NP or the HP diet. With all three diets the mean survival time of NX rats was less than that of 2K rats on the same diet. The mean survival time of NX rats on the HP diet was also less than that of NX rats on the LP or NP diet. Proteinuria preceded the fall in GFR in NX rats. The proteinuria was most severe in NX rats on the HP diet, but only moderate with the LP diet. We conclude that, in a rat strain not very prone to develop renal lesions, the GFR of a solitary kidney eventually declines. An LP diet postpones but does not prevent the decline.

Aging↗

The effect of a reduced sodium intake on post-renal transplantation hypertension in rats.

In an experimental model of post-renal transplantation hypertension in rats, we studied the effect of a reduction of sodium intake on the development of this type of hypertension. Systolic blood pressure, plasma renin concentration and renal function were measured regularly in recipients of an allogeneic kidney transplant that had previously undergone active immunological enhancement. Transplant recipients on a normal diet showed a rise in systolic blood pressure during the second week after transplantation. The systolic blood pressure of recipients on a low sodium diet remained normotensive throughout the 15 weeks follow-up period. The plasma renin concentration was low in the hypertensive recipients on a normal diet, as compared with unilaterally nephrectomized controls. Although the plasma renin concentration of recipients on a low sodium diet fell below that of unilaterally nephrectomized controls on a low sodium diet, it was higher than that of recipients on a normal diet. The renal function of transplant recipients was greatly reduced compared with that of control rats. The glomerular filtration rate was reduced to a greater extent than the effective renal plasma flow. In a separate experiment it was revealed that a similar reduction in the glomerular filtration rate of kidneys permanently damaged by temporary ischaemia did not result in an increase in the systolic blood pressure. Survival up to 6 weeks after transplantation was the same for both groups of recipients. Recipients on a low sodium diet, however, showed a better 15 weeks survival, probably owing to the absence of hypertension in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

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Allogeneic kidney transplantation after active immunological enhancement: a model to study post-transplantation hypertension in rats.

A model was developed to study post-transplant hypertension after allogeneic kidney transplantation between two inbred normotensive rat strains. Prolongation of graft survival was achieved by 'active immunological enhancement'. Renal function, systolic blood pressure and plasma renin concentration were determined. The systolic blood pressure started to rise in the second week after allogeneic transplantation. The glomerular filtration rate was impaired to a greater extent than the effective renal plasma flow. Histopathological changes occurred indicating immunological reactions in the renal graft. The plasma renin concentration was lower in transplant recipients than in controls. We hypothesize that retention of sodium is mediately involved in the post-transplant hypertension observed in this model.

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