Evaluation of a high sodium-low potassium cold-storage solution by the isolated perfused rat kidney technique

The isolated perfused rat kidney (IPK) model was used to assessinitial renal function after 24 h preservation in 3 differentcold storage solutions: EuroCollins (EC), a solution preparedaccording to the formulation of Belzer's solution (High-K⁺ UW)and a high Na⁺-low K⁺ Belzer UW solution (High Na⁺ UW). GFR and FR_Na were measured after 24 h cold storage in each ofthe solutions during 60 min, and were compared to values obtainedin a control group in which renal function was measured immediatelyafter the kidneys had been harvested. ATP and CP were measuredin fresh renal tissue, in kidneys preserved for 24 h in eachsolution, in control IPK, and in reperfused IPK after they hadbeen preserved for 24 h. Main results showed that preservationin either solution caused a dramatic decrease in GFR and inFR_Na within the first 60 min following reperfusion of cold-storedkidneys. However FR_Na was significantly higher in the High-Na⁺UW group. ATP and CP content were decreased to 10% of basalvalues in all experimental groups after cold-storage. Normothermicreperfusion of IPK after cold-storage induced a restorationof ATP levels, but CP content decreased further. There was nosignificant difference in ATP and CP content between cold-storagesolutions, nor any correlation between metabolic and functionalparameters.     

Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction.

BACKGROUND: Renal myofibroblast infiltration has been shown to be strongly associated with renal function decline in several chronic renal diseases. The purpose of the present study was to investigate whether early detection of myofibroblast infiltration using alpha-smooth-muscle actin (alpha-SMA) expression in time-zero biopsies predicts renal allograft dysfunction. METHODS: We studied renal tissue from 38 renal transplant patients from whom biopsies had been taken after vascular anastomosis during transplantation to ascertain whether myofibroblasts infiltration predicts renal graft survival. Immunohistochemistry was performed on time-zero biopsies to determine alpha-SMA expression, and this was compared to annual glomerular filtration rate (GFR) variation and other parameters including cold ischaemic time (CIT), donor and recipient age, number of acute rejections, and delayed graft function (DGF). GFR was measured by inulin clearance during of 3 years of follow-up after the transplantation. Progressors were defined as patients with an annual GFR decline >5 ml/min/year. RESULTS: We found a significant correlation between interstitial alpha-SMA expression in time-zero biopsies and GFR evolution during the post-transplantation course (r=0.60, P<0.001). Although progressors had greater interstitial alpha-SMA expression than non progressors (7.9+/-0.7 vs 4.3+/-0.4%), they showed only a tendency towards higher glomerular alpha-SMA expression. In addition, progressors had more interstitial fibrosis in time-zero biopsies than non-progressors. There was no relationship between alpha-SMA expression and CIT, donor and recipient ages, number of acute rejections, and occurrence of DGF. CONCLUSION: This study suggests that alpha-SMA evaluation in time-zero biopsies, especially the combination of alpha-SMA expression and interstitial fibrosis, can strongly predict chronic renal allograft dysfunctions.     

Outcome of cadaver kidney transplantation in small children

Cochat P, Castelo F, Glastre C, Martin X, Stamm D, Long D, Lavocat M-P, Hadj-Aïssa A, Lyonnet D, Floret D. Outcome of cadaver kidney transplantation in small children. Acta Pædiatr 1994;83:78–83. Stockholm. ISSN 0803–5253 Small children have often been reported to have poor outcome after kidney transplantation (KT). Recent reports from North America have shown that the use of living-related donors improves patient and graft survival. We report the experience in one centre of primary cadaveric KT using sequential immunosuppression in nine children aged 8–30 months and weighing 5.4–9.8 kg; donors were 0.7–12.3 years old. Four patients had pre-emptive KT and the other five were on peritoneal dialysis; the mean ± SD waiting time was 2.0 ± 2.4 months. Perioperative care has been published previously. The surgical approach was intraperitoneal if the aorta and vena cava were used (n= 7) and extraperitoneal for common iliac vessels anastomosis (n = 2); the duration of surgery was 3.5 ± 0.9 h and the time for vascular anastomosis was 32 ± 6 min. The recipients received ATG, azathioprine, prednisone and delayed administration of cyclosporin A. The patients were followed for 12–98 (median 41) months and showed good graft function (inulin clearance 63–100 ml/min/1.73 m²); only one child with recurrent haemolytic uraemic syndrome lost his graft three months post-transplantation and died after he had received a second graft. None of the recipients required post-transplant dialysis; arterial hypertension involved four children and was related to graft artery stenosis in two. Growth improved by 0.24 ± 0.48 SD score of height per year. Compared to earlier reports on cadaver transplantation in small children (about 40% graft survival after five years) and to the outcome of chronic peritoneal dialysis, the present results are better and appear to be similar to those obtained with living-related donor transplantation.     

Influence of hemodialysis on total and free malondialdehyde measured by a new HPLC method

Accurate evaluation of oxidative stress is needed for patients on chronic hemodialysis (HD), as cardiovascular risk level seems related to it. Oxidative stress is often evaluated by measuring an end product of lipoperoxidation named malondialdehyde (MDA). However, the most common technique for measuring MDA, the Thio Barbituric Acid Reactive Substances method (TBARS), is known to be sensitive but poorly specific. We measured true total and free plasma MDA in fifty-four unselected patients on long-term HD, before and after HD sessions, by a new, highly specific HPLC method. Total and free MDA were higher before than after dialysis. Essentially, free MDA was decreased by HD but its fractional decrease was lower than that of urea or creatinine. This confirms that, in fact, free MDA is more or less bound to low molecular weight compounds and/or suggests that MDA may be produced mainly during HD sessions. We propose this new tool to further explore the relationship between oxidative stress, HD and true MDA.     

Outcome of preemptive renal transplantation and pretransplantation dialysis in children

  The present study compares the outcome of 40 children (39%) transplanted without prior dialysis, i.e., preemptive transplantation (PET), with 63 children (61%) transplanted after a variable duration of dialysis, i.e., pretransplantation dialysis (PTD). The two groups were matched for recipient and donor age and for immunological risk factors. There was no statistical difference in the time to first acute rejection episode nor in the number of acute rejection episodes during the 1st year after renal transplantation. In the PET group, 78% of the recipients received blood transfusion versus 92.5% in the PTD group (P<0.05), and the average number of blood units per patient was 3.2 and 7.8, respectively (P<0.05). Arterial hypertension was found in 55% of the patients in the PET group versus 73% in the PTD group (P<0.05). The number of functioning grafts at the end of the study period was 87.5% in the PET group and 73% in the PTD group (NS). The major cause of graft failure was vascular thrombosis in the PET group (3/5) and chronic allograft rejection in the PTD group (10/17). In the PET group, the actuarial graft survival rate was 100%, 84%, 81%, and 76% at 1, 3, 5, and 7 years, which was not statistically different from the PTD group at 1, 3, and 5 years (98%, 91%, and 73%, respectively) but there was a significantly lower graft survival (59%) after 7 years in the PTD (P<0.05). The 7-year actuarial patient survival rate was 97% in the PET group and 90% in the PTD group (NS). In the PTD group, children on dialysis for less than 1 year (group 1, n = 25) were compared with those on dialysis for more than 1 year (group 2, n = 38). Arterial hypertension was noted in 40% of patients from group 1 and 65% from group 2 (P < 0.05) ; there was no significant difference in graft loss rate. In conclusion, these results confirm PET as the preferred approach rather than PTD in children who need renal replacement therapy. Received September 22, 1995; received in revised form and accepted February 19, 1997     

Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4±2.2 (±SD) years after chemotherapy (total cumulative dose: methotrexate 41±31 g/m², ifosfamide 39±14 g/m², cisplatin 674±188 mg/m²) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m² in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications. Received September 29, 1997; received in revised form December 12, 1997; accepted February 18, 1998