Restoration Of Renal Function Research Articles

Altered Vascular Homeostasis in Type 2 Diabetic Nephropathy

Type 2 diabetic nephropathy is a primary cause of ESRD worldwide. Therapeutic strategy in patients with microalbuminuric or macroalbuminuric type 2 diabetic nephropathy usually fails to restore renal function but merely slows the renal disease progression. In contrast, a recent study implies that the restoration of renal function as well as renal perfusion can be accomplished in early stage of type 2 diabetic nephropathy (normoalbuminuria) by correcting the hemodynamic maladjustment in renal microcirculation with vasodilators. Therefore, we intend to study the mechanism of vascular homeostasis to explain why treatment in the late stage of diabetic nephropathy during microalbuminuria or macroalbuminuria fails to enhance renal perfusion or restore renal function. The results indicate that such therapeutic failure in late-stage type 2 diabetic nephropathy likely relates to multiple defects in vascular repair, namely deficiencies in angiogenic factors such as endothelial progenitor cell, angiopoietin-1, flt-1 receptor, as well as elevated levels of antiangiogenic factors such as angiopoietin-2 and KDR.

Nutritional Consequences of Renal Transplantation

Successful kidney transplantation leads to restoration of renal function. Some metabolic disorders from chronic renal failure may persist and new metabolic abnormalities can develop (obesity, diabetes, hypertension, bone disease, and anemia). Additionally, influence of immunosuppressive drugs (corticosteroids, cyclosporine A, tacrolimus, and rapamycin) may aggravate the course of diabetes, hypertension, and dyslipidemia. Nutritional management of renal transplantation is divided into the pretransplant period, transplant surgery, and early and late posttransplant period. Patients in the pretransplant period in dialysis treatment may develop protein-energy malnutrition and negative nitrogen balance, with loss of lean body mass and fat deposits. Nutritional management in the early posttransplant period with a functioning kidney graft necessitates fluid and electrolyte balance control with protein intake of 1,2/kg BW/day and 30-35 kcal/kg BW/day. In a nonfunctioning kidney graft, dialysis treatment continues and the therapeutic dose of immunosuppressive drugs must be reduced. The principal objective in the late posttransplant period is the maintenance of optimal nutritional status. Nutrition is important in managing obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension. Other posttransplant conditions for which diet and/or nutritional supplements may be beneficial include hypomagnesemia, hypophosphatemia, hyperuricemia, hyperkalemia, hyperhomocysteinemia, chronic renal allograft failure, renal anemia, and renal bone disease.

Restoration of renal function in zebrafish models of ciliopathies

The ciliopathies are a class of rare human genetic disease whose aetioligies lie in defective primary cilia. Typical ciliopathies include Bardet–Biedl syndrome (BBS), nephronophthisis (NPHP), Jeune, Joubert, oro-facial-digital (OFD1) and Meckel (MKS) syndromes. All ciliopathies have the common denominator of renal disease, often including tubular cysts. In this study, we have modelled a range of ciliopathies in zebrafish and shown in all cases that knocking down these genes causes cystic lesions in the kidney. We have identified two drugs, rapamycin and roscovitine, which ameliorate the renal phenotype, both morphologically and functionally. This is the first study in which zebrafish has been used to identify potential therapeutic modalities for ciliopathic renal disease, and the results pave the way for further investigations in mammalian models.

Renal Artery Stent Placement for Restoration of Renal Function in Hemodialysis Recipients with Renal Artery Stenosis

Renal artery stent placement to treat renal artery stenosis (RAS) in patients undergoing hemodialysis is not performed commonly. We present our outcomes of discontinuation of hemodialysis after treating patients with RAS by stent placement on acute (< or =30 days of hemodialysis) and chronic hemodialysis (>30 days). A retrospective study was conducted in 16 patients (nine men) with an average age of 74.6 years +/- 10.6 (range, 49-86 y) who underwent treatment of 22 RAS for acute renal failure (n = 8) or uncontrolled hypertension with chronic hemodialysis (n = 8). The average follow-up was 448 days +/- 450 (median, 363.5 d; range, 6-1,583 d). The primary outcome consisted of discontinuation of hemodialysis, death, and transplantation. Secondary endpoints included restenosis, changes in blood pressure (and use of medications), and estimated glomerular filtration rate (eGFR). After the stent procedure, eight patients were able to discontinue hemodialysis and remained free from dialysis over a mean period of 564 days +/- 533. The predictors of discontinuation of hemodialysis were 24-hour proteinuria, eGFR before renal artery stent placement, and size of the kidney on ultrasound studies (P < .05 for all three). There was no difference in patients who were undergoing acute versus chronic hemodialysis. There were three minor complications, and one patient died 6 days after the procedure because of multiple cardiovascular problems. Renal artery stent placement for the treatment of RAS in patients receiving hemodialysis can result in discontinuation of hemodialysis in patients with low proteinuria level and adequate kidney size and eGFR.

Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Dermopathy

Nephrogenic systemic fibrosis (NSF) is a rare, idiopathic systemic fibrosing disorder that is predominantly characterized by a clinicopathologically distinct symmetric dermopathy and debilitating joint contractures. The condition affects patients with renal insufficiency and appears to show improvement with prompt restoration of renal function. Although NSF was initially reported in the United States as nephrogenic fibrosing dermopathy, it has subsequently been described in patients in Europe and Asia. More than 215 cases of NSF have been reported in the nephrogenic fibrosing dermopathy/NSF registry that is currently maintained at the Yale University. Recent reports suggest a possible etiologic link between systemic administration of gadolinium-containing magnetic resonance imaging contrast agents in patients with renal insufficiency and the development of NSF.

Nephrogene systemische Fibrose - eine neue interdisziplinäre Herausforderung

Nephrogenic systemic fibrosis (NSF) - previously termed nephrogenic fibrosis dermopathy - is a newly recognized disorder occurring only in patients with renal failure. Exposure to gadolinium-containing contrast agents used for magnetic resonance imaging has been associated with subsequent development of NSF. This disease is characterised by swelling and tightening of the skin, mostly at the limbs. In addition, internal organs may be involved, which may ultimately cause death in rare cases. Skin biopsy showing fibrous tissue and spindle cells positive for CD34, and factor XIIIa as well as CD68-positive macrophages confirms the diagnosis. The main therapeutic goal is restoration of renal function by renal transplantation or recovery from acute renal failure, whenever possible. There are few data regarding other measures. The best available evidence for some therapeutic effect relates to physiotherapy and extracorporal photopheresis. Gadodiamide and gadopentetate-dimeglumin must not be used in stage 4 and 5 renal failure. Other gadolinium-containing contrast media must be used with extreme caution in patients with advanced renal failure.

Anuric acute renal failure and pulmonary oedema: A case for urgent action

Atherosclerotic renovascular disease (ARVD) is a common manifestation of atheromatous disease. Whilst it usually displays a chronic and asymptomatic course, it is increasingly recognised as playing a significant pathophysiological role in a number of clinical presentations. Anuric acute renal failure (ARF), due to thrombotic renal artery occlusion (RAO) or progression to critical narrowing, however, is a rare complication of this. We report a patient who presented with anuric ARF and pulmonary oedema secondary to bilateral renal artery disease (one chronic RAO, one highly critical renal artery stenosis (RAS)). She showed a good response to renal revascularisation with restoration of renal function, even when this was performed after six days of anuria.

Does renal ageing affect survival?

The effects of ageing on progressive deterioration of renal function, both in human and experimental animals, are described elsewhere, but the effect of renal damage on overall survival and longevity is not yet clearly established. The wild-type animals of various genetic backgrounds, fed with regular diet, overtime develop severe age-associated nephropathy, that include but not limited to inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis. Such renal damage significantly reduces their survival. Reducing renal damage, either by caloric restriction or by suppressing growth hormone (GH)/insulin-like growth factor-1 (IGF-1) activity could significantly enhance the longevity of these animals. Available survival studies using experimental animals clearly suggest that kidney pathology is one of the important non-neoplastic lesions that could affect overall survival, and that restoration of renal function by preventing kidney damage could significantly extend longevity. Careful long-term studies are needed to determine the human relevance of these experimental studies.

Effect of dopamine and metaraminol on the renal function of patients with septic shock

Vasoactive drugs are often necessary for reversing hypotension in patients with severe infection. The standard for evaluating effects of vasoactive drugs should not only be based on the increase of arterial blood pressure, but also on the blood flow perfusion of internal organs. The effects of dopamine and metaraminol on the renal function of the patients with septic shock were investigated retrospectively in this study. Ninety-eight patients with septic shock were divided into three groups according to the highest infusing rate of metaraminol, with the lightest infusing rate of (0.1 - 0.5, 0.6 - 1.0, > 1.0) microgxkg(-1)xmin(-1) in group A, B and C respectively. Urine output, mean arterial blood pressure (MAP), heart rate (HR), urine output, blood urea nitrogen (BUN), creatinine (CRE), urine albumin (U-ALB), urine beta(2)-microglubulin (Ubeta(2)-MG) and Apache III scores were recorded. Before antishock therapy, hypotension, tachycardia and oliguria occurred to all the 98 patients with septic shock and CRE, BUN, U-ALB, Ubeta(2)-MG and Apache III scoring were abnormal in most cases. With the antishock therapy, MAP, HR, urine output, BUN and CRE in all patients returned gradually to normal (P < 0.05 or < 0.01 compared to those before antishock therapy). U-ALB, Ubeta(2)-MG output and Apache III scoring also reverted but remained abnormal (P < 0.01 compared to those before antishock therapy). No statistically significant differences in the changes of these indices with the time existed among the three groups (P > 0.05). Dopamine and metaraminol when applied to the patients with septic shock could effectively maintain the circulatory stability and promote restoration of renal function.

The Impact of Living Donor Kidney Transplantation on Markers of Cardiovascular Risk in Chronic Kidney Disease Patients

Background: Kidney transplant (Tx) patients present a reduced cardiovascular (CV) mortality in comparison to the dialysis population, but in comparison to the general population, it is still several-fold higher. Methods: We studied risk factors for CV disease in a group of 38 patients (50% males, median age 36 years) who underwent a living donor Tx at the baseline and after 3 ± 1 and 9 ± 2 months. Results: The prevalence of overweight increased from 26 to 54% after Tx (p < 0.001). The mean systolic blood pressure decreased significantly after the Tx (148 ± 27.6 vs. 126 ± 12.7 mm Hg). There was a significant increase in LDL (97 ± 30 vs. 114 ± 35) and hematocrit (33.8 ± 4.4 to 42 ± 5.7%) levels and a significant reduction in fibrinogen levels (394 ± 91 vs. 366 ± 100 mg/dl) after 9 months as compared to the baseline. Obesity and dislipidemia were significantly correlated with inflammation. Significant changes in left ventricle mass index (293 ± 116 vs. 241 ± 96) were observed after the Tx. Patients with a low glomerular filtration rate (GFR) in the follow-up evaluation presented higher LDL (128 ± 7 vs. 99 ± 7 mg/dl; p < 0.05) and higher fibrinogen levels (399 ± 21 vs. 332 ± 22 mg/dl; p < 0.05) compared to patients with a high GFR. Conclusion: Most of the risk factors analyzed (particularly the uremia-related) improved after the renal Tx, which could justify the positive impact of Tx on the development of CV disease. Inflammation and dyslipidemia were related to renal dysfunction after the Tx, suggesting that complete restoration of renal function may have an impact on reducing CV mortality in CKD patients treated with renal Tx.

Renal Outcome of Neonatal Renal Venous Thrombosis: Review of 28 Patients and Effectiveness of Fibrinolytics and Heparin in 10 Patients

Neonatal renal venous thrombosis is a rare disorder that can result in severe renal damage. To evaluate the experience over 10 years and review the effectiveness of fibrinolytic and/or heparin therapy, chart reviews were performed for newborns with renal venous thrombosis. PATIENTS, INTERVENTIONS, AND OUTCOME MEASURES: Twenty-eight newborns with renal venous thrombosis were treated at Children's Hospitals and Clinics of Minnesota and Fairview University Medical Center from 1991 to 2001. Unilateral involvement was noted in 25 neonates (89%) and bilateral involvement in 3 (11%). Unilateral renal venous thrombosis affected mostly term infants, whereas 2 of 3 infants with bilateral renal venous thrombosis were <32 weeks' gestational age (birth weight: 745-1505 g). One mother had antiphospholipid syndrome. Of 11 neonates evaluated for congenital thrombophilia, 1 had the factor V Leiden mutation. Ten neonates received either unfractionated or low molecular weight heparin for 3 days to 7 months. Three infants with unilateral renal venous thrombosis treated with heparin alone did not seem to benefit from such therapy. Seven neonates were treated with fibrinolytics and unfractionated heparin (4 neonates with unilateral renal venous thrombosis and 3 with bilateral renal venous thrombosis). Treatment with fibrinolytics did not result in restoration of renal function in the 4 neonates with unilateral renal venous thrombosis but was associated with return of almost normal function in the 2 neonates with bilateral renal venous thrombosis who received fibrinolytics immediately after renal venous thrombosis diagnosis. Two neonates treated with fibrinolytics suffered bleeding complications at the area of adrenal hemorrhage. Two neonates (not treated for renal venous thrombosis) died as a result of underlying disease. Most neonatal renal venous thrombosis is unilateral and does not respond to fibrinolytic therapy and heparin. The use of fibrinolytics may prevent chronic renal failure in neonates with bilateral renal venous thrombosis if begun within 24 hours of diagnosis. Fibrinolytic therapy, however, is associated with a risk of bleeding, specifically if there is an associated adrenal hemorrhage.

Comparative effects of selective and non-selective nitric oxide synthase inhibition in gentamicin-induced rat nephrotoxicity

Different nitric oxide synthase (NOS) isoforms are found in the kidney. Some studies provided evidences that increased endothelial NOS (eNOS) activity leads to restoration of renal function after injury, but activation of inducible NOS (iNOS) aggravates renal failure. In the present study, the beneficial effects of selective iNOS blockade in gentamicin (GM) induced nephrotoxicity have been investigated. Four groups of rats were studied. Untreated control rats received saline. In GM group, GM was injected (IV, 4 mg kg(-1)). In GM + L-NAME group rats received L-NAME (N-omega-L-arginine methyl ester, a non-selective NOS inhibitor) simultaneously with GM (IV, 30 mg kg(-1)). Additional doses of L-NAME were administered 2 and 4 h after GM (IP, 30 mg kg(-1)). In GM + L-NIL group rats were treated by N-imino-ethyl lysine (L-NIL, a selective iNOS inhibitor). First dose (IV, 3 mg kg(-1)) administrated simultaneously with GM. Next doses (IP, 3 mg kg(-1)) were administered 2 and 4 h after GM. In all groups, serum and urine creatinine levels were measured. Creatinine clearance was calculated and considered as an estimation of glomerular filtration rate (GFR). Urine N-acetyl-b-D-glucose aminidase (NAG) activities were also determined. After experiments, kidney sections were histologically studied. Selective iNOS inhibition by L-NIL prevented the GM-induced decrease in GFR and increase in creatinine levels, while complete non-selective NOS inhibition by L-NAME aggravated the GFR reduction, elevation of creatinine levels and enzyme release (P < 0.05). Histological studies showed that GM-treated kidneys had evidences of tubular damages and these damages were less evident by the administration of L-NIL. In conclusion, selective inhibition of iNOS may prevent GM-induced nephrotoxicity, whereas non-selective inhibition of NOS aggravates it.

Nephrogenic Fibrosing Dermopathy

Nephrogenic fibrosing dermopathy (NFD) is an acquired, idiopathic, chronic, progressive eruption of the skin sometimes accompanied by systemic fibrosis that occurs in the context of renal failure. The age of patients with NFD ranges from 8 to 87 years at the time of onset, with a mean age of 46.4 years. Most cases have been reported in the US and Europe, but recently cases have also been reported in India. About 175 cases have been noted in a registry established for NFD patients. Even in the setting of renal disease, NFD still occurs rarely and its cause is unknown. Patients present with hard, indurated, sometimes peau d'orange plaques. They often show a distinctive physical appearance, with elbows and knees angled inward, and most patients complain of a loss of range of motion. Histology demonstrates thickened collagen bundles with surrounding clefts, mucin, and a proliferation of fibroblasts and elastic fibers, sometimes with reticular, dermal, large epithelioid or stellate spindle cells. Fibrosis of NFD can affect the internal organs and thus the term nephrogenic systemic fibrosis has been used by some analysts to describe this fibrosing process. The fibrosis of NFD appears to be due to the effects of a cell referred to as the circulating fibrocyte. Rare cases of partial-to-complete spontaneous resolution have been reported in the absence of specific therapy. Treatments yield inconsistent results and include restoration of renal function, extracorporeal photopheresis, photodynamic therapy, high-dose intravenous immunoglobulin, and other immunosuppressive therapies.

Predictive Factors in Chronic Allograft Nephropathy

Chronic allograft nephropathy (CAN) is characterized by progressive renal dysfunction leading in many cases to graft loss. The pathogenesis of CAN involves both immune and nonimmune factors. Concerning immune factors, one of the most remarkable predictors of CAN is acute rejection, which is associated with a worse prognosis if there are multiple episodes or when late onset occurs. Delayed graft function is also a major risk factor for CAN because of a correlation between late restoration of renal function after transplantation and long-term decreased graft survival. High creatinine levels at 6 months and 1 year after transplantation, proteinuria, viral infections, and cardiovascular risk factors are additional significant parameters for the development of CAN. Recent findings suggest that a high renal segmental arterial resistance index measured by Doppler ultrasonography in intrarenal vessels is associated with poor allograft function. Moreover, the study of patient genetic profile represents a new approach to identify predictive factors for CAN.

Effect of Renal Transplantation on Biomarkers of Inflammation and Oxidative Stress in End-Stage Renal Disease Patients

Chronic kidney disease patients have a high prevalence of inflammation and oxidative stress, and this has been associated with the excess cardiovascular morbidity and mortality observed in this population. Because maintenance hemodialysis is ineffective in controlling these factors, we hypothesized that restoration of kidney function by transplantation would be required to improve uremic inflammation and oxidative stress. This was a prospective cohort study evaluating time-dependent changes in biomarkers of inflammation and oxidative stress before and after renal transplantation. Nineteen end-stage renal disease (ESRD) patients (age 38.3+/-13.7 years, 58% male, 95% white, 21% diabetic) undergoing living-donor renal transplantation were enrolled. C-reactive protein (CRP), interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, protein-associated carbonyl content, and F2-isoprostanes were assessed at 1 week pretransplantation and at 1 week and 2 months posttransplantation. Pretransplant levels of the pro-inflammatory proteins IL-6, TNF-alpha, and CRP, as well as the oxidative stress markers plasma protein carbonyls and F2-isoprostanes, were significantly elevated in ESRD patients compared with healthy control subjects. We observed rapid and significant declines in all of these biomarkers after transplantation that persisted for 2 months. Our findings indicate that restoration of renal function by transplantation improves the chronic inflammation and increased oxidative stress associated with uremia, which may contribute to the improved survival afforded to ESRD patients by renal transplantation.

New-Onset Posttransplantation Diabetes Mellitus: Insulin Resistance or Insulinopenia? Impact of Immunosuppressive Drugs, Cytomegalovirus and Hepatitis C Virus Infection

Restoration of renal function may ameliorate uremia induced insulin resistance. Therefore it seems a paradox that new-onset posttransplantation diabetes mellitus (PTDM) is a frequently observed complication after renal transplantation. The incidence varies between 2 and 50% depending on the population under study, criteria for the diagnosis of diabetes and the time of follow up. This review addresses recent findings on transplant specific risk factors and pathogenesis of PTDM after solid organ transplantation, and we focus on the following issues: 1. The relative impact of insulin resistance and insulinopenia in the pathogenesis of PTDM. 2. The role of immunosuppressive drugs with special emphasis on calcineurin inhibitors (cyclosporine A, tacrolimus) and steroids. 3. The possible roles of cytomegalovirus and hepatitis C infections. New-onset PTDM is characterized by a variety of clinical manifestations, ranging from predominantly insulin resistance which can be handled with lifestyle intervention, to beta-cell failure requiring insulin treatment. The etiology is multi-factorial, but diabetogenic immunosuppressive drugs are of major importance. Future studies should therefore address the effects of different immunosuppressive regimens on the incidence of PTDM. In addition, the impact of cytomegalovirus infection and hepatitis C on PTDM needs further evaluation.

Transforming growth factor-β in acute renal failure: receptor expression, effects on proliferation, cellularity, and vascularization after recovery from injury

Transforming growth factor (TGF)-beta1 and a number of TGF-beta-responsive genes are transiently enhanced following induction of ischemic acute renal failure (ARF) in the rat. The mRNA and protein expression of TGF-beta receptors were analyzed in postischemic rat kidneys by ribonuclease protection, in situ hybridization, and immunohistochemistry. TGF-betaRI and -RII were enhanced within 3 days of ischemia-reperfusion (I/R) injury and remained elevated for up 7 days post-I/R; TGF-beta receptor expression was localized primarily in regenerating tubules within the outer medulla. A neutralizing TGF-beta antibody exacerbated cellular proliferation observed on day 3 postischemia but had no effect on day 1 or 2. TGF-beta antibody treatment had no measurable effect on loss of renal function or the restoration of renal function during the recovery response for up to 35 days postsurgery. However, ischemic injury resulted in modest renal hypertrophy that is due, in part, to in an increase in the number of interstitial cells in the postischemic kidney. Immunohistochemistry showed that several of these cells stained positively for the fibroblast-specific marker, S100A4 positive. Anti-TGF-beta treatment substantially attenuated the renal hypertrophy, interstitial cellularity, and S100A4-positive cells present at 35 days post-I/R. Finally, TGF-beta immunoneutralization attenuated the loss of renal vascular density following recovery from I/R injury. These data suggest that the TGF-beta/TbetaR system is enhanced in the postischemic kidney. However, the current study failed to identify a prominent role for this system in the repair of proximal tubules following ARF. In contrast, the activation of this system may play an important role in the long-term structure of the postischemic kidney by influencing microvascular structure and interstitial cellularity.

Urinary Transforming Growth Factor-β1 Excretion in Renal Allograft Recipients During the Early Post-transplantation Period

Background. Transforming growth factor-β1 (TGF-β1), the major fibrogenic growth factor, is implicated in the pathogenesis of renal scarring in experimental and clinical nephropathies as well as in chronic allograft nephropathy. In this study we examined the pattern of changes of TGF-β1 excretion in the urine and the sites of TGF-β1 expression in the kidney of transplanted patients during the early post-transplantation period. Methods. Eighteen renal allograft recipients were included in the study. In all patients urinary TGF-β1 levels were determined by ELISA in sequential measurements during the first two postoperative months and compared to that of 14 healthy subjects. The renal expression of TGF-β1 protein was studied in 4 patients that underwent a biopsy of the transplanted kidney at the same period. All patients were treated with prednisolone, cyclosporin, and mycophenolate mofetil. Results. Urinary TGF-β1 levels were increased during the first postoperative days. Although they were gradually reduced during the first two post-operative months, they remained significantly higher compared to those of normal subjects (580 ± 148 ng/24 h vs. 310 ± 140 ng/24 h p<0.01). The decline of urinary TGF-β1 excretion followed that of serum creatinine. TGF-β1 protein expression was identified within the cytoplasm of tubular epithelial cells of transplanted patients. Conclusions. Elevated urinary TGF-β1 levels are observed during the early post-transplantation period in renal allograft recipients and are maintained high even after restoration of renal function to normal.

Total serum bile acids in renal transplanted patients receiving cyclosporine A.

A direct relationship between serum bile acids (SBA) and hepatic and hepatobiliary dysfunction has been demonstrated. However, there is little evidence that SBA are related to renal insufficiency. In a previous study, we showed that hemodialysis patients with advanced chronic renal failure (ACRF) have an increase of SBA in predialysis and a decrease in postdialysis. Consequently, it was assumed that the restoration of renal function in transplanted patients might decrease SBA levels. Transplanted patients receiving cyclosporine A (CyA) were studied by monitoring CyA and SBA levels to determine if a probable relationship exists between renal function, CyA treatment and SBA levels. SUBJECTS. SBA levels were determined in 15 recently transplanted patients receiving CyA for 18 months and longer. In addition, 22 renal patients transplanted not less than 6 years ago were also included in the study and were characterized as the stable group. Five patients from this group received mycophenolate or azathioprine instead of CyA as immunosuppressant. In addition to SBA and CyA, creatinine, cholesterol, y-GT, viral markers and triglycerides were also determined in all patients. A significant and constant increase in SBA levels was observed in the recently transplanted group. However, after 18 months, SBA levels gradually decreased to those of patients considered stable under CyA treatment. In both recently transplanted and stable patients who received CyA, SBA values remained higher than normal, but stable patients under mycophenolate or azathioprine treatment showed no such increase. In recently transplanted patients, in patients studied for 18 months post transplant and in stable patients receiving CyA, the increase of SBA levels might be related to CyA treatment. This effect might be attributed to its cholestatic effect and also to a modification in uptake, metabolism, synthesis and excretion of SBA in the hepatocyte. These conclusions are supported by the results obtained in stable transplanted patients without CyA treatment showing normal SBA levels.

Restoration of renal function in shock by perfusion of the renal artery with venous blood: a counterintuitive approach.

Acute renal failure (ARF) in low-flow states may be reversed by increasing renal perfusion. When hemodynamics are maximized, renal perfusion can only be improved by shunting a higher proportion of cardiac output to the kidney; however, in low-flow states, this reduces already compromised systemic pressure and perfusion to other organs. Increasing perfusion using venous blood (VB) would be an attractive option because decreased systemic pressure and perfusion to other organs could be avoided. However, it is not known whether VB can provide adequate oxygen delivery to restore or maintain renal function. We studied whether antegrade VB perfusion of the kidney via the renal artery would restore urine output (UO) and glomerular filtration rate (GFR) in hypoperfused ARF. Shock was induced in six dogs via a hemorrhagic protocol resulting in a systolic blood pressure of 50-70 mm Hg, a mixed venous oxygen saturation of 25% to 40%, and a UO <10% of baseline. After 60 mins of shock, the left renal artery was cannulated under fluoroscopy and perfused at pressures of 100-150 mm Hg for 30 mins with VB drawn from the vena cava and delivered by an extracorporeal pump system. The right kidneys were controls and remained hypoperfused. All VB-perfused kidneys recovered renal function after a sustained period of shock and marked oliguria: UO from 0.7 +/- 1.6 mL/hr to 101 +/- 58 mL/hr (p <.01); GFR from approximately 0 to 70.3 +/- 55 mL/min (p =.04). The control kidneys' UO (0.7 +/- 1.6 mL/hr) and GFR (0 mL/min) remained unchanged throughout the study. The experimental kidneys were able to extract oxygen from VB (O2 saturation, 31 +/- 7% to 16 +/- 4%; p =.01). When flow is controlled, kidneys in hypoperfused ARF can extract sufficient oxygen from antegrade VB perfusion to restore renal function (UO and GFR).