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PubMed2001

Why is erythropoietin made in the kidney? The kidney functions as a critmeter.

Erythropoietin is distinct among the hematopoietic growth factors because it is produced primarily in the kidneys rather than the bone marrow. The kidney functions as a critmeter in that it senses oxygen tension and extracellular volume. By regulating red cell mass through erythropoietin and plasma volume through excretion of salt and water, the kidney sets the hematocrit at a normal value of 45%. This is not a random number, but a value that maximizes oxygen delivery to peripheral tissues. The ability of the kidney to coordinate these two volumes to generate a hematocrit of 45% establishes it as the logical site for erythropoietin production. The kidney has the unique ability to translate a measure of plasma volume as tissue oxygen pressure required to regulate erythropoietin production. I hypothesize that the critmeter is a functional unit that regulates the hematocrit. The critmeter is found at the tip of the juxtamedullary region of the cortical labyrinth in the kidney, where erythropoietin is made physiologically. Renal vasculature and nephron segment heterogeneity in sodium reabsorption generate the marginal tissue oxygen pressure required to trigger the production of erythropoietin. The balance of the oxygen consumption for sodium reabsorption and the oxygen delivery to the proximal tubule is reflected by the tissue oxygen pressure that determines red blood cell mass adjusted to plasma volume. Factors that affect blood supply and sodium reabsorption in a discordant manner may modulate the critmeter (eg, angiotensin II). Examples of clinical disorders caused by dysfunction or resetting of the critmeter are described.

Anemia↗
PubMed1995

Effect of pre-treatment with desferrioxamine and mannitol on radical production and kidney function after ischaemia-reperfusion. A study on rabbit kidneys.

The effects of pre-treatment with mannitol and the iron chelator desferrioxamine on oxygen radical formation and glomerular and tubular function after ischaemia in the rabbit kidney were studied. Radicals were measured with ESR and spin trapping. At reperfusion after 60 min of renal ischaemia there was a significant increase in the production of free radicals in the venous effluent from the kidney. Administration of either mannitol or desferrioxamine given before ischaemia and before recirculation reduced the radical production significantly. The iron chelator appeared to be more effective. Glomerular function measured 48 h after reperfusion was significantly better after pretreatment with desferrioxamine and mannitol compared with mannitol alone. Tubular function did not differ between the two pre-treatment groups.

Animals↗
PubMed2000

Do regular high protein diets have potential health risks on kidney function in athletes?

Excess protein and amino acid intake have been recognized as hazardous potential implications for kidney function, leading to progressive impairment of this organ. It has been suggested in the literature, without clear evidence, that high protein intake by athletes has no harmful consequences on renal function. This study investigated body-builders (BB) and other well-trained athletes (OA) with high and medium protein intake, respectively, in order to shed light on this issue. The athletes underwent a 7-day nutrition record analysis as well as blood sample and urine collection to determine the potential renal consequences of a high protein intake. The data revealed that despite higher plasma concentration of uric acid and calcium, Group BB had renal clearances of creatinine, urea, and albumin that were within the normal range. The nitrogen balance for both groups became positive when daily protein intake exceeded 1.26 g.kg but there were no correlations between protein intake and creatinine clearance, albumin excretion rate, and calcium excretion rate. To conclude, it appears that protein intake under 2. 8 g.kg does not impair renal function in well-trained athletes as indicated by the measures of renal function used in this study

Adult↗
PubMed1988

Iloprost preserves kidney function against anoxia.

Tissue protective activity of iloprost against anoxia was studied in the isolated perfused rabbit kidney. Addition of iloprost to the perfusion medium at concentrations between 10(-9)-10(-7) M attenuated the release of noradrenaline due to periarterial stimulation and decreased urine outflow. Iloprost also caused a concentration-dependent decrease in perfusion pressure. The potentiation by angiotensin II of the vasoconstriction due to periarterial stimulation and increase in urine volume were also decreased by further addition of iloprost into the medium. Iloprost at concentrations below 10(-7) M did not alter the vasoconstrictor effect of exogenously applied noradrenaline. UK 38 485, a powerful thromboxane A2 synthetase inhibitor, significantly suppressed the vascular but greatly potentiated the diuretic effects of angiotensin II. In kidneys exposed to anoxia for 24 hours in Krebs medium, the vascular and diuretic effects of angiotensin II and the release of noradrenaline due to periarterial stimulation were significantly diminished. In addition, interation between UK 38 485 and angiotensin II in both perfusion pressure and urine volume was also reduced after anoxia for 24 hours. On the other hand, no significant loss was observed in all investigated parameters measured in this study, in kidneys exposed to anoxia for 48 hours in the presence of iloprost. From these results it was concluded that iloprost preserves kidneys functionally against anoxia and possible mechanisms of this effect are discussed.

Animals↗
PubMed1990

Kidney function and cardiovascular risk factors in non-insulin-dependent diabetics (NIDDM) with microalbuminuria.

Microalbuminuria in non-insulin-dependent diabetes (NIDDM) is a strong predictor of increased mortality. The major causes of death are cardiovascular, whereas end-stage renal failure is of low frequency. To define kidney function and the presence of some assumed cardiovascular risk factors, we compared a group of 19 microalbuminuric NIDDM patients (M), of mean age (+/- SD) 65 +/- 4 years, and known duration of diabetes 8 +/- 7 years, with 19 randomly selected matched normoalbuminuric patients (N). Seven microalbuminuric patients (P) were also studied. Glomerular filtration rate (GFR) did not differ between N and M, whereas kidney volume was increased in M (260.3 +/- 54.1 ml 1.73 m-2) compared to N (220.4 +/- 44.8 ml 1.73 m-2; P = 0.018). The frequency of cardiac disease increased with increasing albuminuria. Glycaemic control did not differ between the groups, but fasting plasma C-peptide levels increased from 2.8 +/- 1.1 micrograms l-1 in N, to 3.7 +/- 1.7 micrograms l-1 in M (P = 0.08), and to 4.2 +/- 1.9 micrograms l-1 (P = 0.03) in P. The lipoprotein profile showed no significant differences, although the LDLcholesterol/HDLcholesterol (LDL-C/HDL-C) ratio tended to rise. A significant correlation was found between C-peptide and LDL-C/HDL-C (r = 0.5; P less than 10(-3]. In conclusion, GFR was not increased, and did not differ between N and M, whereas kidney volume was enhanced in M. Several assumed cardiovascular risk factors showed values of M intermediate between those of N and P.

Aged↗
PubMedDate not supplied

Liver and kidney function in patients undergoing mechanical circulatory support with Jarvik-7 artificial heart as a bridge to transplantation.

Changes in liver and kidney function were reviewed in 32 patients who received a Jarvik-7 total artificial heart (TAH) as a bridge to transplantation. Preoperatively, seven (22%) had significant isolated kidney dysfunction, five (15%) had isolated liver impairment, and 13 (41%) had combined disorder, affecting 25 (78%) of the 32 recipients. Immediately after TAH implantation, vigorous diuresis occurred, and biochemical indices improved in 17 patients: 71% of isolated kidney, 60% of isolated liver, and 38% of combined organ disorder were reversed irrespective of severity in preoperative dysfunction. In contrast, urine output remained poor, and biochemical indices continued to deteriorate in 15 patients regardless of preoperative status; as a result, kidney (28%), liver (17%), and combined organ failure (33%) accounted for a total of 78% of failure in this series. Although preoperative liver and kidney dysfunction were frequent and severe, they did not correlate with postoperative functional recovery and later transplantation. Recipient body size and initial postoperative urine output were found to be the variables discriminating patients with or without subsequent transplantation. Because liver/kidney failure remained as the leading cause of death, knowledge of the underlying cause of the organ failure would increase the success of TAH as a bridge to transplantation.

Acute Kidney Injury↗
PubMed1992

Influence of oral contraceptive agents on kidney function and protein metabolism.

The present study was an investigation of the effect of oral contraceptives on kidney function as well as a brief examination of protein metabolism, since glomerular filtration rate depends to a large extent on daily protein intake. 28 healthy women not taking contraceptives and 46 healthy women (aged 20-28 y) on one of three different types of oral contraceptive (combination preparations) were investigated [Minulet/Femovan, Marvelon, Diane]. In all groups on oral contraceptives the endogenous creatinine clearance was significantly increased. The potassium excretion rate was significantly elevated in the groups taking Marvelon and Diane, and the sodium excretion rate was significantly increased in those on Minulet/Femovan and Diane. In all groups on contraceptives the albumin excretion rate was numerically but not significantly elevated. No significant differences were found in the daily oral protein intake or the nitrogen excretion rate on comparing the groups taking contraceptives with the control group. However, the ratio nitrogen excretion rate/daily protein intake was significantly increased in those on Minulet/Femovan and Diane. The study has shown that besides their various effects on renal tubular function, oral contraceptives are able to increase the glomerular filtration rate, and certain types have a protein catabolic effect.

Adult↗
PubMed2000

Kidney function in cyclosporine-treated paediatric pulmonary transplant recipients.

BACKGROUND: Lung or heart-lung transplantation is a useful therapy in life-threatening pulmonary disorders during childhood. Cyclosporine A is a major immunosuppressive treatment but has a number of adverse effects including nephrotoxicity. There have been no reports on the long-term evolution of renal function in a large series of paediatric pulmonary transplantation recipients. METHODS: We examined 19 patients followed up for at least 3 years after pulmonary transplantation. The mean time of follow-up was 5.36 years. Kidney function was evaluated by calculation of glomerular filtration rate (GFR) according the Schwartz formula. RESULTS: The GFR was normal before transplantation in all patients. The short-term evolution of GFR was marked by a significant drop during the first and until the 6th month. Then, regardless of the level reached at the end of the 6th month, the GFR remained stable in all patients except one until the end of follow-up. At the end of follow-up, 31% had normal GFR, 57% had mild chronic renal failure, and 5% had advanced renal failure. Hypertension was frequent and associated with renal failure. CONCLUSIONS: Paediatric pulmonary recipients showed evidence of long-term cyclosporine A-associated nephrotoxicity. Most of this toxicity occurred during the first 6 months.

Adolescent↗