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Uptake and release of amino acids by normal and remnant kidneys: studies in the isolated perfused rat kidney.

In order to evaluate the capacity of normal and remnant kidneys to take up and release amino acids when plasma concentrations are increased above normal levels, we have determined the simultaneous net uptake or release of eight representative amino acids using the isolated perfused rat kidney model. Eight normal and five partially infarcted kidneys from Sprague-Dawley rats were perfused with Krebs-Ringer's bicarbonate buffer containing glucose 8 g/100 ml albumin and amino acids at concentrations approximately 10 times above normal plasma levels. Urine was collected every 15 min for 75 min, and perfusate samples were obtained at the midpoint of each urine collection. Amino acids were measured by gas-liquid chromatography. During perfusion, there was substantial net utilization of asparate, proline, alanine, and glycine by normal kidneys. In remnant kidneys the net uptake of amino acids tended to be lower than that of the normal kidneys. The fractional excretion of most amino acids by remnant kidneys was significantly higher than that of controls. These studies demonstrate the substantial capacity of the kidney to take up or release amino acids when presented with an increased load. The findings suggest that the fractional reabsorption of amino acids by residual nephrons of remnant kidneys is decreased.

Amino Acids↗

Contribution of native kidney function to total glomerular filtration rate after combined kidney-pancreas transplantation.

BACKGROUND: Combined kidney-pancreas transplantation (CKPT) with its associated euglycemia has been shown to prevent or reduce recurrent diabetic nephropathy in the renal allograft. There has been no evaluation of residual native kidney function after CKPT. The purpose of this study was to determine whether native kidney function may be present in diabetic recipients years after CKPT. METHODS: Between 1986 and 1992, 37 patients with type 1 insulin-dependent diabetes mellitus with renal failure underwent CKPT. In each case, a single native nephrectomy was performed. We studied 16 patients who had continuing renal and pancreas function more than 4 years after CKPT. Fourteen diabetics with a functioning renal allograft but no pancreas function were used as a control group. Simultaneous renal scans (technetium-99m diethylenetriamine pentaacetic acid) of the native and transplanted kidneys were obtained with a dual-head scintillation camera. Total glomerular filtration rate (GFR) was determined from the rate of clearance of the tracer from the extracellular space measured for 2 hr with an ambulatory renal monitor. RESULTS: The study groups had similar pretransplant characteristics. At the time of the study, the mean serum creatinine level was not significantly different in the CKPT and control groups (1.7+/-0.7 vs. 1.5+/-0.3 mg/dl, respectively). In the CKPT and control groups, total GFRs were 70.1+/-33 vs. 72.1+/-16.5 ml/min (NS), allograft GFRs were 63+/-34.2 vs. 70.4+/-16 ml/min (NS), and native kidney GFRs were 7.1+/-7.2 vs. 1.7+/-1.9 ml/min (P < 0.05), respectively. In both groups, there was a significant correlation between total GFR and allograft GFR (P < 0.001), but not between total GFR and native kidney GFR. Significant single native kidney GFR (more than 8 ml/min) was found in 7/16 (44%) patients in the CKPT group, but in none of the controls. CONCLUSIONS: These results suggest that residual native kidney function can be present and contribute moderately to total GFR after CKPT. Euglycemia after CKPT may have a protective role in native kidneys.

Adult↗

Altered expression of Na(+)/H(+) exchanger isoforms 1 and 3 in clipped and unclipped kidneys of a 2-kidney-1-clip Goldblatt model of hypertension.

BACKGROUND: Functional differences between the clipped and unclipped kidneys in a 2-kidney-1-clip (2K-1C) hypertension model have been reported. However, the molecular basis of these changes is poorly understood. OBJECTIVES: Expression of NHE-1 and NHE-3 isoforms and sodium pump activity (PNP), and their modulation by blood pressure (BP), PGE(2) and TXB(2) were examined in the kidneys of 2K-1C rats treated with cilazapril for short- (4 and 24 h) and long-term (7 days) periods. METHODS: 2K-1C rats were divided into two groups. Group 1 (short-term) animals were treated with a single dose of cilazapril for 4 or 24 h. Group 2 (long-term) animals received a daily dose of cilazapril for 7 days. 2K-1C animals receiving water served as clipped controls, and sham-operated animals were normal controls. Western blot analysis was used to estimate the protein levels and ELISA for PGE(2) and TXB(2). RESULTS: Levels of NHE-1 and NHE-3 protein in the unclipped kidneys of both treatment groups were increased, whereas levels of alpha-actin, PNP activity and crude microsomes remained unchanged. These changes were significantly reduced by long-term, and not by short-term treatment with cilazapril. In group 1 clipped kidneys, NHE-3 and alpha-actin proteins were increased, and crude microsomes and PNP activity were decreased. In group 2 clipped kidneys, both NHE-1 and 3 isoforms were induced, whereas PNP activity was decreased. Cilazapril did not reverse the changes in the clipped kidneys in both groups, but reduced the crude microsomes. Group 2 unclipped kidneys showed hypertrophy, which remained unaffected by cilazapril treatment. Induced levels of BP, PGE(2) and TXB(2) in both groups were reduced significantly except for the 24-hour post-cilazapril treatment. CONCLUSIONS: These findings demonstrate a differential expression of NHE-1 and NHE-3 isoforms which is dependent on the rise in BP, PGE(2) or TXB(2) in the long-term treatment group, but not in the short-term treatment group. Thus, the changes in NHE isoforms and sodium pump activity, together, contribute to functional differences that exist in the 2K-1C kidneys.

Angiotensin-Converting Enzyme Inhibitors↗

Odd-skipped related 1 is required for development of the metanephric kidney and regulates formation and differentiation of kidney precursor cells.

Formation of kidney tissue requires the generation of kidney precursor cells and their subsequent differentiation into nephrons, the functional filtration unit of the kidney. Here we report that the gene odd-skipped related 1 (Odd1) plays an important role in both these processes. Odd1 is the earliest known marker of the intermediate mesoderm, the precursor to all kidney tissue. It is localized to mesenchymal precursors within the mesonephric and metanephric kidney and is subsequently downregulated upon tubule differentiation. Mice lacking Odd1 do not form metanephric mesenchyme, and do not express several other factors required for metanephric kidney formation, including Eya1, Six2, Pax2, Sall1 and Gdnf. In transient ectopic expression experiments in the chick embryo, Odd1 can promote expression of the mesonephric precursor markers Pax2 and Lim1. Finally, persistent expression of Odd1 in chick mesonephric precursor cells inhibits differentiation of these precursors into kidney tubules. These data indicate that Odd1 plays an important role in establishing kidney precursor cells, and in regulating their differentiation into kidney tubular tissue.

Animals↗

Regulation of glomerular TGF-beta expression in the contralateral kidney of two-kidney, one-clip hypertensive rats.

Previous studies have demonstrated that angiotensin II stimulates expression of transforming growth factor-beta (TGF-beta) in cultured renal cells. To investigate whether similar mechanisms are operative in vivo, glomerular TGF-beta mRNA expression was investigated in two-kidney, one-clip (2-K 1-C) hypertensive rats. Glomerular TGF-beta1 transcripts were elevated in the clipped kidney 6 d, but not 3 d, after surgery. Later, during the course of the disease (21 to 35 d), TGF-beta1 mRNA was upregulated in contralateral kidneys compared with sham-operated control kidneys. There was no difference in plasma TGF-beta1 levels between 2-K 1-C rats and controls. Treatment with the AT1 receptor antagonist losartan, as well as with triple therapy (hydralazine, reserpine, and hydrochlorothiazide), started 1 d after clipping, significantly reduced systolic BP in hypertensive rats at day 21 after clipping. Both treatments were equally effective in preventing the increase in glomerular TGF-beta1 mRNA and protein expression in the contralateral kidney at day 21. In a second set of experiments, interventional treatment with losartan or triple therapy, starting 14 d after surgery, was investigated. This treatment for 3 wk significantly reduced the increase in TGF-beta1 expression in the contralateral kidney. At day 35 after clipping, considerable glomerular damage and sclerosis were present, mainly in contralateral kidneys. Interventional treatment with losartan or triple therapy partly prevented this glomerular damage of the contralateral kidney. The data demonstrate that TGF-beta1 expression in the contralateral kidney in 2-K 1-C rats is regulated by the increase in systemic BP rather than by direct effects of angiotensin II.

Animals↗

[Renal function of contralateral kidney after total or partial removal of kidney with ectopic ureter].

The effects of partial or total removal of the kidney with ectopic ureter on the contralateral kidney were evaluated using DMSA renal uptake rate on 8 patients. After partial nephrectomy on 6 cases, the affected residual kidneys showed significant decrease in DMSA renal uptake rate in 2 cases in which the extirpated kidneys had normal renal tissue in part but did not show significant change in DMSA uptake rate in 4 cases in which the extirpated kidneys were dominated mainly with dysplasia. Post-operative increase in DMSA uptake rate of the contralateral kidneys were significant in 3 of 4 patients who had the operation before they became 2 years old. In 2 of these 3 cases, pre-operative scintigram showed extremely low rate of DMSA renal uptake. Four cases aged 2 years old and over did not show post-operative increase in the uptake rate. As we have previously reported on the cases with hydronephrosis, these results suggest that 1) existence of obstruction caused by ectopic ureter inhibit the development of the contralateral kidney and 2) the growth of the kidney can resume the release of that obstruction, if the release is made while the kidneys are still in developing stage.

Child↗

Kidney function after radical nephrectomy: assessment by quantitative SPECT of 99mTc-DMSA uptake by the kidneys.

UNLABELLED: To determine the function of the remaining contralateral kidney after the removal of a functioning kidney, 30 consecutive patients (18 men, 12 women; average age, 67 y; age range, 34-87 y) who were undergoing unilateral radical nephrectomy were evaluated by sequential quantitative 99mTc-dimercaptosuccinic acid (DMSA) SPECT (QDMSA) studies. METHODS: The 30 patients were undergoing radical nephrectomy for renal tumors. The first study was done before surgery. Follow-up studies were performed 2-23 mo after surgery. Clinical evaluations and determinations of serum creatinine level were performed at the same time as the QDMSA studies. RESULTS: The relative contribution of the resected kidneys to the global renal function before surgery was 43.2% +/- 7.3%. After surgery the uptake of the remaining kidney increased from 13.4% +/- 4.0% to 18.3% +/- 5.8% (t = 5.7; P = 0.0000). The relative function of the remaining kidney increased from 56.8% +/- 7.1% to 79.1% +/- 23.6% (t = 4.9; P < 0.0001) of the global renal function before nephrectomy. Increases in the renal volume (from 211 +/- 62 cm3 to 229 +/- 68 cm3; t = 4.5; P = 0.0001) and in the percentage injected dose per cubic centimeter (%ID/cm3) of the remaining kidney (from 0.066 +/- 0.02 % ID/cm3 to 0.085 +/- 0.03 %ID/cm3; t = 4.6; P = 0.0001) were associated with this change. Nine patients had 2 follow-up studies performed 3-4 mo after surgery and 12-14 mo after surgery. The volume of the remaining kidney (209.22 +/- 46.20 cm3 versus 217.88 +/- 58.85 cm3; t = 0.962; P = 0.364), the %ID/cm3 (0.09 +/- 0.016 %ID/cm3 versus 0.093 +/- 0.025 %ID/cm3; t = 0.362; P = 0.726), and the percentage uptake (19.26% +/- 4.45% versus 20.11% +/- 7.01%) did not change significantly between these 2 QDMSA studies. CONCLUSION: The results of this study suggest that adaptive changes causing hyperfunction of the remaining kidney may occur after nephrectomy of a functioning kidney in adults. These changes occur soon after surgery, persist for at least 1 y, and are evident on QDMSA studies.

Adaptation, Physiological↗

Effects of dietary supplementation with n-3 fatty acids on kidney morphology and the fatty acid composition of phospholipids and triglycerides from mice with polycystic kidney disease.

The DBA/2FG-pcy strain of mouse has been developed as an animal model for adult polycystic kidney disease and we have determined the effects of feeding an n-3 fatty acid-enriched diet on kidney morphology and the fatty acid compositions of the constituent phospholipid and triglyceride fractions in this strain. Twelve male and female DBA/2FG-pcy mice were fed lab chow or semi-purified diets containing sunflower seed oil (SO) or a n-3 fatty acid-enriched concentrate (MaxEPA) for 60 days. At necropsy, blood and urine samples were taken and the kidneys processed for examination by light microscopy. Gas-liquid chromatography of the fatty acids in the kidney lipids was also performed. Male and female mice fed the MaxEPA-based diet tended to have lower mean kidney weights. Hematocrits, blood urea, and serum creatinine levels were similar among the lab chow-, SO- and MaxEPA-fed groups. All the groups exhibited a moderate hematuria; the incidence of this symptom was lowest in the MaxEPA-fed male animals. Extensive tubular dilatation was apparent in the cortices and medullae from the lab chow-fed animals; these lesions were slightly less severe in the SO-fed group and least severe in kidneys from the MaxEPA-fed animals. By morphometry, the renal area occupied by cysts was also lowest in the male Max-EPA-fed group; females fed the MaxEPA-based diet did not show a marked decrease in the proportion of kidney area occupied by cysts. Fatty acid compositions of the total phospholipid and triglyceride fractions from kidneys of male mice fed the MaxEPA-based diet showed a reciprocal replacement of the n-6 fatty acids with the n-3 fatty acids compared to kidneys from males fed the SO-based diet.

Animals↗

Impairment and recovery of the clipped kidney in two kidney, one clip hypertensive rats during and after antihypertensive therapy.

Earlier experiments have shown that in sodium depleted hypertensive rats with bilaterally constricted renal arteries the arterial pressure normalized after blockade of the renin-angiotensin system; simultaneously acute renal failure occurred. In hypertensive rats with unilateral renal artery stenosis an impaired excretory function of the clipped kidney can be expected, but may not be detectable by conventional tests of renal function. Male Wistar rats with chronic two kidney, one clip hypertension were fed a low sodium diet. After 7 days the rats were treated with vehicle, with the vasodilator dihydralazine, or with the angiotension converting enzyme inhibitor MK 421 for 2 weeks. During the 14-day treatment period a continuous blood pressure reduction was achieved in dihydralazine and MK 421 treated rats. Overall excretory kidney function (plasma creatinine concentration) was well maintained in all three groups until the end of the antihypertensive drug treatment. At the end of drug therapy mean glomerular filtration rates of the left clipped kidneys were significantly lower in both treated groups compared to hypertensive controls, and mean glomerular filtration rate of the left clipped kidneys of dihydralazine treated rats was significantly higher than in MK 421 treated rats: controls (N = 6) 1.03 +/- 0.03, dihydralazine-group (N = 10) 0.28 +/- 0.07, MK 421-group (N = 9) 0.03 +/- 0.01 ml/min. Renal blood flows were comparable in both treated groups. Only the left kidneys of rats treated with MK 421 showed a prominent tubular atrophy. Seven days after declipping of the left renal artery and right nephrectomy a considerable restitution of the tubular structure had occurred in the MK 421-group. The recovery of tubular epithelial cells was paralleled by a rise in glomerular filtration rate: MK 421 group (N = 7) 1.25 +/- 0.08 ml/min. Thus, the clipped kidney in two kidney, one clip hypertensive rats showed functional and morphological signs of impairment when systemic arterial pressure was reduced to the normal range. The alterations of the clipped kidney were most pronounced in rats with renin-angiotensin system-blockade.

Angiotensin-Converting Enzyme Inhibitors↗

Functional preservation of the mammalian kidney. VII. Autologous transplantation of dog kidneys after treatment with dimethylsulfoxide (2.8 and 4.2 M).

This research demonstrates that dog kidneys perfused with dimethylsulfoxide (Me2SO) in likely cryoprotective concentrations (2.8 M) can survive as the sole source of renal support when autologously transplanted. Kidneys were perfused in vitro with Me2SO in one of two vehicles: solution A (K+-Mg2+-rich) or RPS-2 (K+-glucose-rich). Me2SO concentration in the vehicle was gradually increased to maximum (2.8 or 4.2 M) over a period of 28 to 35 min, held for 5-10 min, then decreased over 55-65 min. All groups except one consisted of 5 kidneys perfused at 25 degrees C. Survivors were dogs living 21 days postoperatively. The first group received kidneys perfused with solution A; 5 dogs survived, serum creatinine on day 21 [Cr], [mean +/- SE] = 1.3 +/- 0.1. The second group received RPS-2 kidneys; 4 survived, Cr=1.4 +/- 0.1. The third group received solution A kidneys with 2.8 M Me2SO; 3 survived, Cr=2.7 +/- 1.3. The fourth group received RPS-2 kidneys with 2.8 M Me2SO; 5 survived, Cr=1.2 +/- 0.2. The fifth group received RPS-2 kidneys with 4.2 M Me2SO; 2 survived, Cr=1.7 +/- 0.3. One group of 6 dogs received kidneys perfused at 10 degrees C with 4.2 M Me2SO in RPS-2; one survived, Cr=1.4. Results demonstrate beneficial interaction of vehicle with Me2SO and the efficacy of 25 degrees C perfusion.

Animals↗

Circulating type VI collagen and undulin, in patients with kidney diseases, after kidney transplantation and on hemodialysis.

Chronic kidney diseases are characterized by alterations in connective tissue turnover resulting in fibrosis. We measured circulating peptides related to type VI collagen and undulin in serum and urine of 125 patients with various kidney diseases, on chronic hemodialysis and after kidney transplantation. Using a double-armed ELISA technique (median, 95% CI), normal serum concentrations for type VI collagen were 50 ng/ml [46-63] with no type VI collagen detectable in urine. Normal values for undulin were 215 ng/ml [207-241] in serum and 240 micrograms/d [223-284] in urine. The serum concentrations of undulin were most significantly (477 ng/mg [358-737]) increased in 18 hemodialysis patients. A significant increase (330 ng/ml [306-368]) was also observed in patients with various kidney diseases not requiring dialysis. No differences were found between the various forms of glomerulonephritis, interstitial nephritis and other kidney diagnoses. Although very low in normals (1.16 ml/min [1.05-1.27]) renal undulin clearance was even significantly lower in patients with kidney diseases (0.5 ml/min [0.4-0.6]). Serum concentrations for undulin were in the normal range in the direct postoperative phase after kidney transplantation (207 ng/ml [167-306]), whereas in kidney transplant out-patient levels were elevated to 425 ng/ml [357-563]. There was a slight but significant correlation between serum undulin and creatinine values and between renal undulin clearance and creatinine clearance. Values of serum type VI collagen increased in analogy to those of undulin. We conclude, that type VI collagen and undulin are novel serum parameters of renal extracellular matrix turnover that merit further exploration in patients with chronic kidney diseases.

Adolescent↗

DNA damage and micronuclei induced in rat and human kidney cells by six chemicals carcinogenic to the rat kidney.

Six chemicals, known to induce kidney tumors in rats, were examined for their ability to induce DNA fragmentation and formation of micronuclei in primary cultures of rat and human kidney cells, and in the kidney of intact rats. Significant dose-dependent increases in the frequency of DNA single-strand breaks and alkali-labile sites, as measured by the Comet assay, and in micronuclei frequency, were obtained in primary kidney cells from both male rats and humans of both genders with the following subtoxic concentrations of five of the six test compounds: bromodichlorometane (BDCM) from 0.5 to 4 mM, captafol (CF) from 0.5 to 2 microM, nitrobenzene (NB) from 0.062 to 0.5 mM, ochratoxin A (OTA) from 0.015 to 1.215 microM, and trichloroethylene (TCE) from 1 to 4 mM. Benzofuran (BF), consistent with its carcinogenic activity for the kidney of female, but not of male rats, at concentrations from 0.125 to 0.5 mM gave positive responses in cells from females but did not induce DNA damage and increased the frequency of micronuclei in cells from males to a lower extent; in contrast, it was active in cells from humans of both genders. DNA-damaging and micronuclei-inducing potencies were similar in the two species. In agreement with these findings, statistically significant increases in the average frequency of both DNA breaks and micronucleated cells were obtained in the kidney of rats, given p.o. a single dose (1/2 LD50) of the six compounds, BF in this assay being more genotoxic in female than in male rats. Taken as a whole, these findings give further evidence that kidney carcinogens may be identified by short-term genotoxicity assays, using as target kidney cells, and show that the six chemicals tested produce, in primary cultures of kidney cells from human donors, effects similar to those observed in rats.

Animals↗

Correlation between the biopsies in marginal donor kidneys for transplantation: is it necessary to biopsy both kidneys?

OBJECTIVES: The objective of this study was to analyze the correlation between histological findings in both transplanted kidneys from marginal donors. METHODS: We retrospectively reviewed the histological information on 92 kidneys obtained between January 2001 and January 2004, corresponding to 46 marginal donors. Criteria for biopsy were age greater than 55 years, hypertension, diabetes, and proteinuria. Scores were established by the pathologist including glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis. The score for each lesion was classified as 0 if absent; 1 if <20%; 2 if >20% and <50%; and 3 if >50%. Finally, we defined an index of renal severity damage (RSD) in order to classify the kidneys for single transplantation (0), double transplantation (1), and unsuitable for transplantation (2). RESULTS: Of the kidneys studied, 82.6% of both kidneys showed similar degrees of glomerulosclerosis (<20% in 71.7% and >20% in 10.9%), while 17.4% showed discrepancies (> vs <20%; P=.008). On the other hand, RSD correlated in 82.6% of both kidneys (in 69.6% RSD=0; in 8.7% RSD=1; and in 4.3% RSD=2), while 17.4% showed discrepancies (P=.001). In one case (2.2%), a great discrepancy was observed; one kidney was valid for single transplantation, and the other one not valid for any transplantation, single or double. CONCLUSIONS: This study demonstrated a correlation between the biopsy findings in both kidneys in 82.6% of marginal organ donors. However, in 17.4% of cases we observed discrepancies. The degree of glomerulosclerosis seemed to be a powerful parameter to define renal severity damage. According to these results we would recommend biopsy of both kidneys.

Biopsy↗

Angiotensin II receptor blockade limits kidney injury in two-kidney, one-clip Goldblatt hypertensive rats with special reference to phenotypic changes.

Recent evidence indicates that tubulointerstitial injury plays an important role in hypertensive kidney injury and that phenotypic changes contribute to this pathology. Moreover, angiotensin II is known to be actively involved in the pathogenesis of progressive kidney injury induced by hypertension. The present study was undertaken to see the effect of a newly developed angiotensin II type I receptor (AT1 receptor) antagonist on hypertension-induced kidney injury and to determine the contribution of phenotypic changes to morphologic alterations. Two-kidney, one-clip (2K1C), Goldblatt hypertensive rats (n = 27) were made by clipping the left renal artery. These animals were orally administered 57G709 (a selective non-peptide AT1 receptor antagonist)(10 mg/kg/day), captopril (20 mg/kg/day), or vehicle alone for 23 days beginning 4 weeks after clipping. In the non-clipped kidney of vehicle-treated 2K1 C rats, marked tubulointerstitial injury as well as glomerular sclerosis and/or hyalinosis was found in association with phenotypic changes, as shown by the neoexpression of vimentin in periglomeruli, perivascular walls, distal tubuli, and injured interstitium. Renin expression was markedly suppressed in the non-clipped kidneys of vehicle-treated 2K1C rats as compared with renin expression in normotensive control kidneys of sham-operated rats. Both 57G709 and captopril markedly ameliorated hypertensive kidney injury as reflected by the glomerular sclerosing index and by the tubulointerstitial index as determined by the point-counting method, and this improvement was accompanied by a significant decrease in blood pressure, urinary protein excretion, kidney/body weight ratio, and heart/body weight ratio. In addition, the vimentin neoexpression mentioned above was also suppressed with an inhibition of angiotensin II. These results suggest that in 2K1C Goldblatt hypertensive kidney injury, the AT1 receptor antagonist 57G709 exerts a potent renal protective effect associated with the inhibition of phenotypic changes.

Angiotensin Receptor Antagonists↗

Increased renal function in kidneys with ureteropelvic junction obstruction: fact or artifact? Assessment by quantitative single photon emission computerized tomography of dimercapto-succinic acid uptake by the kidneys.

PURPOSE: We evaluated whether increased differential renal function on the pentetic acid (DTPA) renogram represents elevated renal function in obstructed kidneys. MATERIALS AND METHODS: In 10 patients with unilateral ureteropelvic junction obstruction and a differential function of 53% or greater on the DTPA renogram of the obstructed kidney we performed quantitative single photon emission computerized tomography of dimercapto-succinic acid uptake by the kidneys. RESULTS: The absolute uptake of dimercapto-succinic acid was significantly higher in the obstructed kidneys compared to the contralateral normal kidneys (30.0% +/- 7.8 versus 25.3% +/- 8.2, t = 3.6, p < 0.01, respectively). The elevated absolute uptake in the obstructed kidneys was due to an increased functional volume compared to the contralateral normal kidneys (126.0 +/- 69.7 cc versus 102.3 +/- 59.2 cc, t = 4.4, p < 0.01, respectively). CONCLUSIONS: The results suggest that increased relative renal function in hydronephrotic kidneys due to ureteropelvic junction obstruction is not an artifact of the DTPA renogram. It may represent a compensatory mechanism that sometimes may overcompensate resulting in a paradoxical hyperfunctioning kidney.

Adult↗

[Statins in patients with kidney failure: efficacy, tolerance, and prescription guidelines in patients with chronic kidney disease and renal transplant].

BACKGROUND: Chronic kidney disease (CKD) is extremely common in adults, although often undiagnosed and thus untreated. Cardiovascular disease is the leading cause of death among patients with CKD and reducing its risk in this population is an important priority. Dyslipidemia is almost always present when proteinuria is above 3 gr/24 hours. Roughly two thirds of all patients with end-stage renal failure and kidney transplants suffer from dyslipidemia and should receive lipid-lowering therapy, as suggested by recent Afssaps (French drug agency) and NKF-K/DOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines. We reviewed recent studies on efficacy, tolerability and prescription recommendations of statins in CKD and renal transplant patients. METHODS: We searched Medline, the international medical database, to conduct a systematic review of the literature on the efficacy and tolerability of statins in CKD and renal transplant patients and on specific recommendations for dosage adjustments in this population. RESULTS: The efficacy of statins in decreasing total cholesterol and LDL-cholesterol levels in dialysis and renal transplant patients is similar to that in the general population. On the other hand, large-scale randomized clinical trials among CKD (4D) and renal transplant (ALERT) patients do not demonstrate that statins significantly decrease rates of cardiovascular disease. They have a beneficial effect on proteinuria and lower the rate of kidney function deterioration in patients with dyslipidemia. Early introduction of a statin in transplant patients did not lead to improved kidney function or prevent loss of the graft. Although most statins are not excreted by the kidneys, the dosage of some must be adapted in CKD patients because of pharmacokinetic modifications induced by renal impairment. CONCLUSION: Statins at appropriately adapted doses have the same efficacy in CKD patients as in subjects with normal kidney function, and tolerance is not a problem. Their effectiveness in cardiovascular prevention in this population has not been demonstrated to date. Results about statin-induced kidney protection are encouraging but further and more specific studies are needed.

Adult↗

Changes in patterns of 24-hr heart rate variability after kidney and kidney-pancreas transplant.

BACKGROUND: Transplantation has been shown to improve cardiorespiratory reflex measures of autonomic function. However, there are limited data on how kidney or kidney-pancreas transplantation influence continuous autonomic modulation of heart rate and the clinical utility of 24-hr heart rate variability (HRV) monitoring. METHODS: Ninety nondiabetic kidney and 30 diabetic kidney-pancreas transplant recipients underwent 24-hr Holter monitoring before and again at 6 and 12 months posttransplantation. Tapes were submitted for determination of HRV including interbeat variability (the proportion of adjacent R-R intervals having a difference <50 msec, the SD of all R-R intervals for the entire recording, and the SD of the averages of R-R intervals calculated over 5-min blocks for the entire recording) which is associated with vagal function, sudden death, and circadian function, respectively. Power spectral analysis quantified total neural, sympathetic, and parasympathetic modulation of the heart in ln(msec2). RESULTS: Nondiabetic kidney recipients showed improvement (P< or =0.05) in the SD of the averages of R-R intervals calculated over 5-min blocks (83.2 vs. 95.7 msec) and the SD of all R-R intervals (94.5 vs. 104.4 msec) by 6 months and all groups showed improvement by 12 months. Kidney-pancreas recipients also showed improved total neural (4.35 vs. 4.64) and sympathetic modulation (2.70 vs. 3.13). Kidney-pancreas recipients had significantly poorer values for each measure (P< or =0.05) at all time points. CONCLUSIONS: Cardiac autonomic neuropathy arises in the presence of uremia and diabetes, with severe dysfunction seen when these conditions occur concomitantly. Improvement in cardiac autonomic function follows both kidney and kidney-pancreas transplantation with more pronounced improvement in the circadian measures. Therefore, circadian measures of 24-hr HRV could be used to monitor the restoration of cardiac autonomic function.

Adult↗

Longitudinal Study of the National Kidney Foundation's (NKF) Kidney Early Evaluation Program (KEEP).

In 2000, the National Kidney Foundation implemented the Kidney Early Evaluation Program (KEEP 2.0) to increase awareness of kidney disease among those at highest risk, and improve outcomes through early detection and referral for care. The KEEP 2.0 screening program identified significant numbers of persons with reduced kidney function, with previously undetected kidney disease risk factors, and with inadequate risk factor control. These data support the evolution to KEEP 3.0, which will continue to identify individuals at high risk for kidney disease, and will address the educational needs of health care providers and consumers, given that preventing and managing kidney disease requires their joint effort. Consumers need to embrace lifestyle behaviors that reduce risk, and adhere to medical recommendations in managing their existing conditions. At the same time, providers need to ensure that the latest evidence-based guidelines in diagnosis and treatment are being implemented in their clinical practice. KEEP 3.0 participants will be randomly assigned to one of several educational programs that vary on whether they provide individually tailored or nontailored information, with long-term follow-up for evaluation of clinical outcomes. Tailored programs may be more successful in supporting behavioral change as these consider the individuals' "readiness to change." In addition, participant-identified providers will be randomly assigned to one of several educational protocols designed to provide evidence-based recommendations for clinical and pharmaceutical management of kidney disease and risk factors; these programs vary on whether they require active or passive participation of providers. Analytic evaluations will examine changes from baseline in participant kidney disease and risk factor status during follow-up, and estimate the influence of the various educational protocols on both process of care measures and clinical outcomes.

Cohort Studies↗